SeeSAR changelog


  • Improvements to covalent docking
    • Automatic detection of covalent warheads: SeeSAR now detects 36 most commonly used covalent warheads from input molecules and automatically transforms them to be used for covalent docking resulting in the creation of covalent protein-ligand complexes.
      • The detection and transformation take place in the background once a covalent docking run has been initiated.
      • Users can now avoid the tedious steps of having to manually edit molecules and adding linker atoms [R] at the appropriate location on input molecules.
      • Molecules with linkers [R] are still supported for covalent docking as per usual.
    • Automatic detection protein residues suitable for covalent docking:
      • SeeSAR now detects the residues Cys, Ser, Thr, Tyr, Lys, Gln and Asn in the binding site and prepares them to be anchors for covalent attachment of molecules via docking, in the Docking Mode.
      • Any residue (from the list above) suitable for covalent docking in the binding site is highlighted by a blue translucent capsule on the side-chain at which the covalent attachment could potentially happen.
      • To select one of the residues for covalent docking, a single click on the corresponding capsule is sufficient. The assignment of the residue for covalent docking is visually indicated by the color of the capsule changing to pink.
      • Note: SeeSAR will not determine the compatibility between the selected residue and the molecules in the docking library during the docking. All molecules from the docking library will be docked on the chosen residue.
  • Large-scale docking on external hardware: Introducing the external Docking Mode.
    • The Docking mode switch can now be toggled to the right to find SeeSAR’s new mode for running large scale docking calculations external hardware such as a single powerful machine, or a cluster.
    • The prerequisite for the successful usage of this mode is the configuration of HPSee, BioSolveIT’s high-performance computing framework, which is also introduced along with this release.
    • Once HPSee has been installed on the external server (remote machines, clusters), access to the server can be configured via the newly added “Web Service” option within SeeSAR’s System Settings.
    • The mode accepts a variety of inputs including molecules added from other modes, molecules loaded from external files, and also libraries uploaded to the external server via HPSee.
    • All docking runs on this mode are run on the external hardware configured, and once the run has been initiated, users can switch to other modes in SeeSAR to carry out other tasks.
    • HYDE optimization of the docked poses can also be done on the server if the user wishes by turning on the corresponding automatic calculation in the “Calculations” option in the System Settings.
    • Note: Once a docking run has been initiated on this mode, it is recommended that the binding site of the protein used is not changed.
    • Users are informed of the status of an ongoing docking run via a progress indicator on the play button.
    • Users can cancel a run that has been started by clicking on the orange button which both terminates the run and deletes all results from the server.
    • Users are informed about completion, of their initiated runs via appropriate notification messages delivered via the Message Center.
  • Usability improvements: Enhanced control on color and visibility.
    • The Sequence View from the existing versions of SeeSAR is now more aptly named as the “Target View Control” panel. This section offers improved usability to control the visibility and color of the different components of the target macromolecules loaded into SeeSAR.
    • The self-explanatory dropdown items “Visibility” and “Color” dictate which components on the target i.e., residues, chains, molecules, metals, and surfaces on which the intended color or visibility assignment is to take place.
  • Miscellaneous improvements
    • When loading proteins into the Proteins or the Protein Editor mode, SeeSAR checks completeness of the structure and warns the user via an indicator on the protein entry on the table if the structure is incomplete
    • A warning triangle on the PDB input field is shown if SeeSAR detects that the PDB info database is out of date.
SeeSAR 13 was created to provide users with all tools required to transform their compound into valuable ideas with a single click.

Important note: SeeSAR 13 comes with an updated HYDE chemistry model. Therefore, affinity calculations may vary between version 13 and older version of SeeSAR. If a project created with a previous SeeSAR version is opened in SeeSAR 13, a subsequent rescoring of poses will be required.
  • MedChemesis: Addition to the Inspirator Mode
    The Inspirator mode gets another feather to its hat with the introduction of MedChemesis!
    MedChemesis creates a series of 3D analogs of the ligand in the binding site, applying up to 290 medicinal chemistry-inspired transformations triggered by one click on all molecules added to the Inspirator. MedChemesis facilitates the generation close analogs of input molecules with improved affinity, bioavailability, as well as covering metabolic soft spots, and finding optimal bioisosteric replacements.
    The “Fragment origin” column indicates the type of transformation that has been applied on a particular result molecule.
  • Enhanced protein surfaces
    The surface generation and display which was so far limited to binding sites is now available for the entire protein surface.
    The mechanism to shown protein surfaces has moved from the Visualization Settings on the top right to the Sequence View.
    The visualization differentiates the binding site from the rest of the protein, and provides an array of methods (LogP, Element, Chains, Custom) for coloring the surfaces.
    Surface transparency can also be toggled between transparent and opaque.
  • Enhanced 3D-model-export to PowerPoint
    The export of 3D models from SeeSAR as .glb files to be used in external presentation tools such as PowerPoint has been extended to include the full protein, including ribbons and surface visualizations.
    This extension overcomes the previous limitation where such exports were only limited to molecules and the binding site residues.
  • Improvements to the chemistry model under the hood
    The chemistry model of SeeSAR 13.0 has been updated with the following changes:
    • Revision of VSEPR geometries
    • Adjustment and fine-tuning of bond lengths
    • Improved aromaticity detection
    • Consistent support of transition metal-containing compounds
    • Improved conformations of anthraquinone ring systems
  • Improvements to the docking algorithm under the hood
    • Improvement and unification of polar interactions
    • Improvement to sulfur interactions
    • Improved and unified non-polar interactions
    • Improved numeric stability and platform-independence of the algorithm
    • Improved ranking and re-docking results
  • Improvements to the scoring function under the hood
    SeeSAR 13 ships with HYDE 2.0 bringing along the following improvements:
    • Consideration of sulfur hydrogen bonds as weak polar interactions
    • Consideration of hydrophobic score contributions for all atoms (including polar atoms)
    • Ability to use sphere (Ph4) constraints as post-filters
    • Improved ranking and correlation to experimental results
    • Improved numeric stability and platform-independence of the algorithm
  • Improvements to the 3D-alignment algorithm under the hood
    SeeSAR 13 ships with FlexS 5.0 bringing along the following improvements:
    • Improved, unified polar interactions and non-polar interactions
    • Consideration of hydrophobic atom contributions for alignment
    • Improved alignment results in benchmarking tests
  • Improvements to the fragment-growing algorithm under the hood
    SeeSAR 13 ships with FastGrow 1.1 bringing along the following improvements (requires the latest versions of growing libraries):
    • Revised fragment databases with chair-only conformations
    • SeeSAR 13 ships with a database of database of 12K fragments. Larger fragment databases can be downloaded from our website, free of charge here.
    • Improved and understandable error messages
  • General SeeSAR visualization architecture update
    The 3D rendering mechanism has been foundationally overhauled to a modernized, platform-independent architecture.
    SeeSAR’s underlying user-interface framework has also been upgraded from Qt5 to Qt6. This upgrade comes with a consequence that some older Linux versions are not supported anymore. All users with server licenses must update to the latest Flexlm 11.19.2 license package.
  • Project compatibility
    Users migrating to SeeSAR 13.0 with projects created with earlier SeeSAR versions will be informed that all scores will be reset owning to the major improvements to the molecule-handling, chemistry, and interaction models in SeeSAR 13.0. Users will be provided the opportunity to save a copy of their older projects.
  • User-facing interface improvements
  • Start-screen
    The start screen will not contain the "What's New" slides anymore, but a direct link to the changelog will be available via the new bullhorn-icon on the top right in SeeSAR. In this way, all changes can be systematically documented on the website, and the user has just this one place to be concerned about if they want to learn what’s new!
    The “What’s New” bullhorn-icon will show a “notification dot” to either indicate the availability of a new SeeSAR version, or if the user has not clicked on this button to read the changelog even once.
  • New hot keys Commonly used table actions now have keyboard shortcuts, applicable across all molecule tables:
    • Check molecule - ALT+C
    • Mark as favorite - ALT+F
    • Set molecule as active/inactive – ALT+A
  • Improved handling of Docking and Similarity Scanner inputs
    The input tables in the Docking and Similarity Scanner modes now contain checkboxes enabling selection and deletion of input molecules that are not need for subsequent docking or 3D-alignment calculations.
    This addition overcomes a previously existing bottleneck that all molecules in the input tables were invariably subjected to docking or 3D-alignment calculations.
  • Improved handling of checked molecules
    When molecules are “checked” on any table, an additional indicator on the total number of molecules currently checked is shown on the table header.
    In modes that feature multiple tables (Docking, Similarity Scanner), the user is warned if actions on checked molecules are attempted when molecules in multiple tables are checked.
    This prevents accidental deletion/moving of molecules that the user might have checked at a different part of the table beyond the current view.
  • Improved notification messages:
    The way notifications are delivered in SeeSAR has significantly changed, ensuring that users do not miss important notifications.
    There are fundamentally 2 kinds of notifications that are shown to users a) Infos (blue background) b) Errors/warnings (red or orange background).
    Errors and warnings remain on the screen and have to be explicitly closed by the user.
    There is an indication on the number of messages available in the Message Center.
    Within the Message Center, the user now has the option to either “clear all infos”, or “clear all messages”.
  • Enhanced filtering options
    Three new filters under the banner “combined filters” are available for usage in the Analyzer, enabling quick and efficient filtering of molecules in using the well- known criteria namely:
    • Drug-likeness (Lipinski’s rule of 5)
    • Lead-likeness
    • Fragment-likeness
  • Improved progress visualization
    A visually, and functionally improved progress dialog is introduced. This new progress visualization conveys three different messages related to the progress of a process currently under execution, namely:
    • A pictorial representation of the process running
    • The percentage of the execution completed
    • The estimated time remaining for the execution to finish
  • Improved support for external HYDE-scoring
    The HYDEscorer definition file exports are also available from the Analyzer, and now also include information of all active Ph4 constraints to be used as post- filters for calculations with the HYDE 2.0 command line tool.
    Note: This extended support of using Ph4 constraints is not available in the Binding Site Mode.
  • Introduction of FastGrow to the Inspirator Mode
    The existing growing algorithm of SeeSAR has been replaced by FastGrow. Fastgrow uses a novel, fast, and accurate shape-based algorithm for structure-based growing into binding pockets. Users can screen tens of thousands of fragments within seconds to receive an optimized suggestion that complements the binding site. SeeSAR features a library of 12,000 fragments for growing per default, and a larger, more diverse library with 120,000 is available as download.
    Please note that following pharmacophore constraints cannot be used with FastGrow calculations: Donor acceptor interaction contact, Donor interaction contact, My own SMARTS, and Covalent warhead.
  • Enhancements to the Docking Mode
    Users can now control the allowed conformations of six-membered rings via an additional slider in the pose generation parameters menu.
    The .flexx docking definition file exported from SeeSAR now also takes the number of poses value set in SeeSAR.
    The user-selected value of the allowed six-member ring conformations is also taken into the .flexx definition file exported from SeeSAR.
  • Enhancements to the Similarity Scanner
    Users can now control the allowed conformations of six-membered rings via an additional slider in the Similarity Scanner parameters menu.
    The .flexs definition file exported from SeeSAR now also takes the number of poses and minimum similarity rating values set in SeeSAR.
    The user-selected value of the allowed six-member ring conformations is also taken into the .flexs definition file exported from SeeSAR.
  • Ligand highlights
    If a PDB file loaded into SeeSAR has the "subject of investigation" / "ligand of interest (LOI)" annotation in its entry, it is now indicated via an additional "LOI" column in the ligand extraction step.
  • Users can control the number of solutions to be generated in the Inspirator Mode via a slider mechanism.
  • Users are directly informed that larger fragment files can be downloaded either directly or at a later point of time in the Inspirator Mode.
  • Molecules pushed between modes retain the 3D visibility setting and user-defined colors.
  • SeeSAR now features a ReCore index with 20,000 fragments per standard.
  • After the first execution of a ReCore run in the Inspirator Mode, a "give me more solutions!" button shows up, informing the user that more solutions are available.
The most beautiful version of SeeSAR so far comes with several augmentations
  • Introducing the Similarity Scanner Mode
    The new Similarity Scanner allows users to perform ligand-based drug discovery (LBDD). The underlying algorithm of FlexS aligns molecules based on their shape and molecular features and can be used for virtual screenings when only one or a few known actives are available without the need of a target structure.
  • Molecule table update
    We have revamped the molecule table management. Now, users can conveniently scroll through poses and molecule entries, annotate those, tag actives and non-actives, and compare conformations with a single click. Furthermore, the automatic addition of active/inactive flags to Excel and SDF file exports can be used for external applications and machine learning.
  • Faster generation of 3D coordinates
    Reading molecules with only 2D coordinates (e.g. SMILES) into SeeSAR will now be much faster, since now all available threads are used in the process of 3D coordinate generation.
  • Pharmacophore constraints
    From the available list of Ph4 constraints, "any, also H" has been removed, a new option "donors or acceptors" has been added, and the option "any non-H" has been renamed to "any heavy atom".
  • Improved clash filtering
    Improved clash filtering - now, molecules with three or more orange clashes are considered as red.
  • The filter panel in the Analyzer can now be open just by clicking on the "filter-symbol".
  • All computed BIOSOLVEIT-properties (eg. MW, LogP, TPSA, Hyde- and Optibrium-related) will not be read in from files as additional "file properties" columns but will be recomputed on the fly upon file import.
  • If for some reason the user's tmp directory is almost exhausted, SeeSAR warns the user that further calculations cannot be done since tmp is full.
  • Properties with values which are not whole numbers cannot be filtered with the "=" operator anymore, only the <= and >= operators can be used. So it is not possible to filter for something like LogP = 0.392, however properties whose values are whole numbers can still be filtered by using the "=" operator, e.g. #H-bonds = 4.
  • The color picker dialog has been changed from the Qt-native to the OS-native variant since for some users, the application was intermittently frozen when using the color picker.
The next stage of covalent docking and workflow support for drug discovery campaigns is here.
  • Covalent warhead constraints
    Users have now the possibility to select "covalent warhead" as a pharmacophore constraint feature. The definition covers over 30 well-known covalent warheads (e.g. disulfides, acrylamides, nitriles, etc.) and can be used to place covalent bond-forming functionalities in close proximity to target residues of interest. Users can use this method to dock in-house compounds to simulate initial binding of compounds at the target as groundwork for subsequent covalent docking.
  • Improvement of molecular 2D representation
    Modifaction of molecules will try to keep the preceding orientation of the molecule to avoid flipping. This little but neat feature will make the ligand optimization and brain storming process more didactic during solo sessions and team meetings.
  • Hyde scorer improvement for covalent docking
    Covalent binding side export and binding affinity assessment by Hyde has been tailored and fine-tuned to the newest release of Hyde 1.3. Now users can conveniently perform command line virtual screening and drug discovery compaigns with covalent binding sites and processed ligands.
With the newest update of SeeSAR Hephaestus we take covalent virtual screening to the next level.
  • Covalent Hyde visualization
    Covalent ligands assessed by Hyde received a visual indicator. Users can interpret the complex or predicted binding modes with an alternative representation to the conventional Hyde assessment in the respective modes. ΔG for all covalently bound ligands by Hyde is calculated without the contribution of the covalent bond itself. To take into account that a covalent bound contributes by a great margin to the binding affinity we introduced a boundless lower limit to reflect this in the visualization.
  • SIENA augmentation
    The topological binding site searcher SIENA can now be used to access own in-house PDB structures. With this users can now profit even more from own resources or external data to find suitable structures for further studies. Consider this option to utilize available databases (e.g. homology models, AlphaFold) to expand your search range.
  • Molecule creation from scratch
    Users have the possibility to start molecule edition with a single atom and grow it into desired molecules. This simple yet highly didactic feature can be used for illustrative molecule built-up and creative drug design by both teams, teachers, and students.
  • ECF exports
    Docking and scoring definitions can now seperately be exported for the command line versions of FlexX and Hydescorer.
  • Option to set SeeSAR as standard PDB file opener
    Upon installation or subsequently you can select SeeSAR as your primary software to open stored PDB files. This gives users easy access to directly start their project at a target of interest.
  • Interaction distance measurement
    During pharmacophore definition/application of pharmacophore constraints users have now the possibility to measure the distance between the suggested interaction center and other atoms. This allows fine-tuning of pharmacophore maps and numerical assessment of the topology.
  • Covalent filter
    Within the Analyzer Mode you can now search for covalently bound ligands to seperate those from non-covalent binders.
SeeSAR 11 (codename: Hephaestus) was forged to support drug discovery artisans.
  • Covalent docking
    The docking mode now supports covalent docking. For details how to prepare the ligand and the target, please see below. To covalently dock a ligand, select one previously defined dummy linker (either already present in your structure or defined in the Protein Editor Mode) of a residue and use the covalent docking button in the main tool bar. The docked complexes can be assessed for affinity with HYDE and ranked to allow evaluation of the docked complexes but no affinity ranges are represented in the table. With this we avoid reflecting any misconceptions connected to affinity prediction of covalent ligands.
  • Covalent target selection
    Define a target residue for covalent docking in the Protein Editor Mode. After picking the linking point of your residue, you can replace the selected atom for a linking dummy atom by selecting [R] in the ‘Change element’ section of the main toolbar. Finally, export the protein to make it accessible for covalent docking.
  • Design covalent warheads
    In the Molecule Editor Mode you can select any anchor point of your ligand and introduce a linking dummy atom [R] in the ‘Change element’ section of the main toolbar to prepare it for covalent docking. With this you can design any covalent warhead and dock it directly at your target.
  • In-depth binding site exploration
    The Binding Site Mode now provides detailed information on binding site properties of your target, including topology (surface area, volume), number of H-bond doners and acceptors, druggability, and hydrophobicity.
  • Export 3D scenes
    SeeSAR 11 supports the export of 3D coordinate models of your target-ligand complexes as glb-files (ligand and included residues) to external applications. The models feature visual SeeSAR indicators (HYDE sphere, bond torsions, …) to support fast information processing. This way you can complement your presentations, meetings, websites and discussions with augmented and interactive models accessible through various ways.
  • Capture scenes
    Every visual scene setting can now be saved and restored later. Adjust your scenery and go to the annotation icon to capture what you see. This facilitates sharing of information and storage of important visuals (e.g. figures for publications).
  • Secondary structure representation
    SeeSAR now automatically computes and displays secondary structural elements using the DSSP algorithm from any PDB formatted file, irrespective of its origin, including homology models. Even users' own in-house structures, perhaps lacking such explicit information, will now be augmented with their secondary structural elements displayed as helices, sheets, and coils.
  • Easy molecule import
    Now you can easily drag and drop several molecule files into the loading screen to save precious time.
The latest version of SeeSAR introduces many improvements for faster and even more elaborate results to support you in your drug discovery process.
  • Augmented binding site exploration
    The search for binding pockets similar to the one of your target with the SeeSAR-implemented SIENA technology has been enhanced: Proposed structures are now displayed with their respective description (TITLE entry in the PDB file) for you to easily grasp the results at first sight. Older projects without this information will be automatically updated. Defining a chain as a ligand is no longer handled as a protein change, thus this pdb can still be used for SIENA. Additionally, optional coloring of individual structures allows easy site-to-site comparison. The selected reference proteins are shown in the sequence view dialog. The discovered binding site of interest can also be exported and used as input for the HYDE command line tool.
  • Binding site definition
    The user has the option to select "do not extract a ligand" in the ligand table after loading a PDB file in the protein mode. The "Go" button is always active and a message box pops up after clicking on it if the user did not select anything in the table. SeeSAR now automatically defines a binding site with the extracted ligand, if previously no binding site was defined.
  • Performance boost
    Improvements deep down in the code for all tables let you scroll through ten thousands of ligands in a flash.
Again, we took that extra step and sprinkled a little magic here and there. And the work was worth the hassle: the new SeeSAR version includes addtional features and improvements to further enhance your drug discovery process.
  • H-bond networks
    The new H-bond network assessment provides you with even more information on your target-ligand complexes. The calculations of inter- and intramolecular H-bonds are decoupled from the HYDE assessment, to enable detailed insights into the binding of your molecule. The quality of favorable and less favorable H-bonds can now be visually be differentiated. H-bonds with “good” geometry and topology are highlighted with satured green hues, while “bad” H-bonds are represented in light green. Note that this mandates a recalculation of previously obtained HYDE scores.
  • Protein ensembles
    A junction between SeeSAR and the ProteinsPlus web service from the ZBH Center for Bioinformatics (Hamburg, Germany) has been added to the Protein Editor Mode. The SIENA technology evaluates the available PDB structures searching for binding pockets similar to the one at hand. The special advantage of this technology: the comparison is not only limited to the sequence of the target alone, but additionally involves the overall topology of the binding site – which can lead to unexpected yet valuable results. You get these comfortably aligned and ready for visual inspection.
Once again, following on from a major release, we are pleased to be able to provide you with an update comprising several enhancements both large and small.
  • This release adds some finishing touches to the new, extensive protein editing facilities in SeeSAR. You can now delete entire chains or set short chains to be ligands. All ligands are visible during editing and clashes can be visualized too, to better guide the editing process. You, as the user, also get the final say about which hetero-groups should be considered as covalent binders.
  • During docking, it is often times necessary to be a little more forgiving about clashes, as poses are generated on a coarse-grain grid of torsion angles only. For this reason, we have added clash tolerance as an adjustable parameter in Docking mode.
  • Filtering became altogether more comfortable with this release, as you can now toggle individual filters on or off very simply. It is possible to use sphere constraints more precisely to define pharmacophores, as they can be set to be either optional or essential. Finally, the release includes a new feature to help you position constraints using interaction points as a visual guide — especially helpful for defining constraints on the basis of the binding site.
Our motto for SeeSAR is "fast, visual, easy", and this is exactly why people love working with our 3D modeling platform. With version 10, we are proud to present you a major update! The most visible and striking difference is certainly the brand new design. SeeSAR has matured over the years and many additional functionalities have been added to address your day-to-day 3D modeling needs. So to keep it intuitive, we have redesigned all modes, menus, and buttons to preserve its easy-to-use character. Besides the redesign, we also present these important new features that deserve special attention:
  • Protein Editor mode
    Using features similar to those found in the Editor mode for small molecules, you may change the side-chain of any residue in this mode. Furthermore, you can eliminate unwanted water molecules, ions, ligands, terminal residues, or even entire chains. Protein editing is a really powerful option to overcome any deficiencies there may be in your PDB. For example, you may want to detect the interface of a PPI, or work with a wild type missing a specific mutation, or simply remove a covalent binder.
  • Clipping of surfaces
    Surfaces are essential to get a good sense of the shape and depth of a binding site. However, once you visualize the surface, it inevitably occludes your view. So, we are happy to introduce user-friendly clipping planes for your binding site surface. Through intuitive controls and by initializing the clipping plane optimally through the scene, SeeSAR now offers you an easy-to-use clipping experience, so that you can better visualize your ligand inside the pocket.
  • Other important updates are (A) You may now use your own growing-library in the Inspirator mode. (B) Define your own SMARTS in pharmacophore constraints in order to focus more precisely on what you want or need. Finally (C) Copying molecules between modes just became much faster and is now accompanied by a progress bar.
As you can imagine, a major change like this (editing of the protein) required an update of SeeSAR's internal storage. So, unfortunately, old project files cannot be loaded with this new version. We recommend you save your molecules from old projects to file and re-read them with this SeeSAR 10.
This is more or less a "silent release" that includes numerous improvements to SeeSAR behind the scenes and also two new features for the user. Perhaps you won't notice most of these changes but in case you have stumbled on these things in the past, here are a few examples: We optimized the internal database so that molecules can be moved much more quickly from one data table to another, we fixed a small bug in the ReCore engine, clashes and torsions are calculated automatically together with HYDE and torsion labels are now also available for bonds in new fragments generated in the inspirator.
  • PDB export
    You may now select any pose in any of the data tables and export it together with the binding-site protein as a complex in PDB format. This feature is a bonus for users who wish to post-process results in MD packages that expect this particular input format.
  • Extended licenses
    Since version 9, the new FlexX is integrated into SeeSAR as the Docking mode and can be used with the SeeSAR license. Since version 9.1, the docking calculation set-up can be exported from SeeSAR for separate processing in the commandline version of FlexX, e.g. on a cluster, which until now required a separate license. Your SeeSAR license is now valid for both the GUI as well as bulk docking using the commandline version of FlexX.
Once again, following on from a major release, we are pleased to be able to provide you with an update comprising several enhancements both large and small.
  • Can't remember the exact PDB code? No problem! Find proteins that are available for download from the PDB on the fly using the new keyword search function.
  • You may notice some small redesigns in the GUI: SeeSAR is bursting with icons and while nearly all buttons are icons, not all icons are buttons. The differentiation between buttons and information is now crystal clear. At the same time, very important buttons that switch the display style in data tables and in the sequence view are now easier to understand and have been given more room. Finally, when you reach a "point of no return" like deleting a protein, we ask for your confirmation to prevent any mishaps.
  • The sequence view lets you show and hide protein components (residues, chains, water). A new context menu (right click on the component) now provides additional functions. You may, for example, zoom in on a component in 3D. In Binding Site mode, the context menu also enables you to add and remove individual residues to and from the binding site.
  • The selection of a ligand for the protein definition (after loading a protein) has been simplified. Users told us this was a little tricky as there were multiple choices and the icons were hard to decipher. We DO listen to your feedback: we gave the design an overhaul and ideally you won't even notice this step anymore — it's now so simple!
  • Last but not least, we implemented a new fullscreen mode that uses all of the space on your monitor. This is extremely helpful, particularly when you want to present something to your team or if you work with two monitors and docked out widgets.
Modes – modes – modes. Version 9 represents another major leap in SeeSAR's evolution, fully adopting the 'modes' concept. Molecules can be transferred freely between modes as you carry out various different tasks. This gives you much more flexibility while maintaining a structured overview. To help you keep track of where you are, we distinguish the modes using a beautiful backlit color scheme, focused top center on the mode switch but found throughout the tool to guide navigation.
Alongside this major interface redesign, you'll find many more enhancements in version 9:
  • Full control over your binding site
    Now when you load a protein, you must first define what is protein and what is ligand. After that, you can switch to the new Binding Site mode, where you then have complete control over the binding site definition. Load a molecule as a starting point or find the empty cavities (pockets) in your protein — detected by our DoGSite algorithm — and select residues surrounding the molecule or a pocket. Finally, you can fine-tune the binding site definition manually by clicking on residues in 3D that you would like to include or exclude.
  • Docking reloaded
    If you happen to know the binding mode for one compound in a congeneric series, and you know which fragments you want to keep in place while you dock related compounds, you can now use the new, template-based docking algorithm. This is not only much faster but also more accurate when you already know that the common fragment must stay in position. The new, parallel FlexX 4.0 machinery — at work behind the scenes — can also carry out pharmacophore-based docking. This is NOT just a post-filtering of docking results, but the pro-active generation of docking solutions that fulfill the given constraints. All of this is nicely bundled in the new Docking mode.
  • More helpful gems
    In SeeSAR 9 you can save proteins to PDB file; In Docking mode, you may export the binding site to run XXL docking calculations with FlexX 4 separately on a cluster or in the cloud; Until now, protein surfaces could only be visualized for proteins of limited size — this restriction no longer applies; Also — saving the best little gem for last — you can now just (right mouse) drag and drop a png of your ligand from the 2D widget: the 2D widget context menu also supports sdf or even vector graphics svg formats.
This new version covers a number of enhancements (small and big) in various areas of the application:
  • Improved screen shot options
    SeeSAR-users regularly come up with phenomenal results, however, when it comes to publishing, the tool had it's limitations. Particularly large-scale, high-resolution graphics required a high-resolution display at your desktop. Now – independent of your graphics hardware – you may determine the size and resolution for your screen shot. Give it a try and let us see all those wonderful graphics on your posters, your presentations and in your publications to come.
  • Clash-detection and visualization
    The Lennard-Jones potential shows the very steep curve as two atoms come close, indicating that the smallest deviation from the ideal distance is already heavily penalized. A severe clash is the one force that may easily kill all affinity. Therefore we now report clashes on two levels:
    1. In the molecules table as two new columns with a traffic light indicating no (green), moderate (yellow) and severe (red) clashes separately for intra- and inter-molecular clashes. Note that these properties can be used for filtering as well.
    2. In 3D the visualization of clashes may be switched on with a new function under the visualization settings (top right). When turned on, any moderate to severe clash is indicated with arrows between the atoms involved. Note that this visualization is "live" as you edit molecules.
  • User colors for reference compounds
    Way back, with version 5.5, we introduced the option to select and show multiple molecules (as so-called reference compounds), such that they are kept in place as you browse through your molecules table. Now many users said that it would be nice – for better distinction – if they all had different colors. Your wish is our command and rather than dictating any color, we put you in charge. So now, as you select a molecule to become reference, a colored field appears in the table. You may click on it and select any color you wish for this particular reference.
  • Spotting differences in multiple proteins
    When multiple proteins are loaded, the binding site in 3D usually becomes quite busy. With version 8.0 we bundled all visualization controls in the sequence view. A mouse-over shows you quickly where any residue, molecule, water or chain is located and then you can simply toggle show and hide of the object. In this version we facilitate hiding at once all components that are close to the protein, which was used to define the binding site. This way – with one click – only the significant differences between multiple proteins stay in view, which removes a lot of redundancy and the scene appears much less busy.
Significant changes and improvements in SeeSAR demand another major release and version 8 well deserves to be a major update. The biggest change is that we now provide full protein visualization support. While the focus of the tool is for the most part still on the defined binding site, you can now...: see the whole protein in all its glory! As always, a major update means that HYDE scores must be re-calculated to stay in line with the changes made in the underlying structures. We certainly believe that these enhancements are well worth it:
  • Improved alignment
    So far aligning and superposing binding sites for multiple proteins has been restricted to very similar protein structures only. Quite a few users have provided their feedback where this has failed — thank you for that. We have re-worked the alignment engine and are able to handle all of the borderline cases we have seen. While the alignment is still suited to homologous proteins and similar binding sites only (we simply don't want you to compare apples with oranges), the limitations are far less severe, so we are quite confident that we have found a great compromise.
  • Full protein support in the seqence view
    The sequence view has been enhanced a great deal. Most notably all components of proteins are visible and not just the components of the defined binding site (individual proteins, residues, small molecules, metals, waters, and chains). You can restrict the sequence view to show the defined binding site only (as before) but you now also have access to everything — plus a very convenient search feature.
  • Bundled visualization controls
    So far the visibility of protein components could be toggled (show/hide) in two unrelated locations that were far apart in the UI: (a) the visualization settings top right and (b) the sequence view. For your convenience we have bundled all these visualization controls in the sequence view. In each of the tabs, protein components that can be shown or hidden are represented by items which all display the same behavior — namely: mouseover highlights the corresponding components in 3D and click toggles their visibility. A new reset view button allows you to go back to the visualization defaults.
  • Enhanced pharmacophore handling
    Pharmacophores (namely sphere constraints) may be defined and used in different parts of SeeSAR. They can currently be used in the inspirator and for filtering in the molecules table, while in an upcoming version of SeeSAR they will be available for docking as well. The handling of sphere constraints has now been centralized so that the list of defined constraints is available globally in SeeSAR. Once a constraint has been defined, it is available to use everywhere. In addition, we have improved the consideration of sphere constraints during growing in the inspirator. Whereas the pharmacophore was previously applied as a post-filter to the final set of results, it is now actually used to guide the growing algorithm in generating suitable solutions that meet the constraint.
  • Inspiration for covalent binders
    You may now also load covalent binders into the inspirator which means you can design — in a de novo fashion — covalent inhibitors using the core replacement, fragment merging and fragment growing technologies that are available in this mode. Particularly in conjunction with the enhanced application of pharmacophores (c.f. above), the growing option for covalent binders has become quite a powerful tool.
Ease of use once again forms the focus of this new SeeSAR version 7.3. We found that the growing amount of features (editing, ReCore, docking, growing, ...) — and buttons that go with them — have impacted the clear and intuitive use a little. So we have focused on fixing this and are proud to present this update with loads of usability enhancements.
  • Mode switch
    So far, the molecules table has, in a sense, been the "main table". A selection of molecules from this table could be used to launch the editor (or Inspirator). Once you were done with your design work, you had to leave the editor again and return to the molecules table. Now, while the idea is still the same in principle, you are much less restricted: You can simply switch from mode to mode, like walking from one room to another. And when you leave one room, its contents stay there waiting for you when you come back. As before, you must use a molecule or selection of molecules to add new molecules to a different mode using the table menus. Give it a try — you will love it.
  • Automated calculations
    It's a typical love-hate thing: One user loves the ultimate convenience of having everything calculated when they save their edited molecule to the table, while the other hates waiting for time-consuming calculations that they are not interested in. We have implemented a "happy medium" solution to give you the best of both worlds. In the settings dialog you can find a new tab called "Calculations" which lists various actions. Here you can choose whether to switch calculations on or off to produce your own automated workflows for any of these actions.
  • Context menus
    Every molecule in a table or grid has its own menu. When the molecule is clicked, the menu button becomes visible and another click on the button opens the menu. Context menus are commonplace in software as a quick way to access functionality, so we have now added context menus to the tables and grids. It's quite intuitive and even saves a click every time.
  • Button groups
    The table menus were bursting with functionality (12 buttons at the last count), which started to get a little confusing. To remedy this, we have grouped together the buttons for calculations, for adding molecules to a different mode, and for sending molecules to file, StarDrop or trash. This has left 7 visible buttons in the molecules table menu giving a much clearer overview. The functions in the table menu are available for selections of molecules — this hasn't changed. But we have now adopted another common behavior in software, namely that functionality is only available once you have made a selection via checkboxes. So first select molecules using the checkboxes or the checkbox menu in the table header and then you can access the table menu functionality. This way, we have also saved the click in a sub-menu that was previously necessary to chose between checked or all molecules, streamlining the path to your goal.
  • Export to Excel
    This is a much requested functionality now available in SeeSAR — but you need to know where to find it! It is accessible via the export to file button in the molecules table menu. You now have the choice of exporting to either SDF or XLSX. The export to Excel feature exports all your checked molecules — including their associated data and 2D image — into the famous Office format. Note: try out the checkbox menu in the table header to check all your molecules with just one click.
  • Saving settings
    While several settings in SeeSAR relate to your specific work environment (e.g. 1 monitor vs. 2), other preferred settings depend on the particular project you are working on. The former are saved as user settings (the layout, the appearance, window size etc.), while the latter are now saved in the project file (backbone on/off, show/hide specific amino acids, your filters). This way you can take a break at any point and later safely resume your work without losing any of your settings.
Get fresh inspiration from this huge update of SeeSAR! We realized, on the one hand, that the functionality of the editor was growing and growing, making it more and more complicated to use. On the other hand, access to the full functionality of ReCore demands a different kind of user interface. So we "took the bull by the horns" and, akin to the editor, created the new Inspirator which you can use to do:
  • Core replacement
    This feature is the same but with a much improved UI. You are able to directly select and visualize the bonds that will be clipped to carve out a core fragment for replacement. The clipped bonds now remain in place (even while you define sphere constraints) up until you define a new query. Also the display of results is much enhanced, as you can see the new core fragments highlighted in 2D as well as in 3D. For reference, your query molecule stays visible as well.
  • fragment linking and merging
    You may of course launch the Inspirator with more than just one molecule. In this case, you can define bonds to clip on different molecules, thereby requesting linker fragments that will connect the remaining pieces. Note that it is not mandatory to clip a terminal part of each molecule to create the query, you may replace a core part in one and connect it to another fragment at the same time.
  • Fragment growing
    This was possibly the most frequently requested functionality in ReCore: Cut just one bond and grow onto this bond using a fragment library of typical side chains. In this way, you can, for example, reach out to nearby subpockets. The new growing algorithm can very quickly scan through a (for now) ready-made library of typical fragments. You may of course define sphere constraints at the same time in order to target particular locations in the binding site. Note that the new growing feature requires the download of a new ReCore index from here!
  • Other enhancements
    • The biggest other enhancement is the new "Sequence View" window. You will have noticed that the binding site visualization dislog was always a bit crowded. As a first step towards a fully featured protein sequence view, the visualization of all binding site components (amino acids, ligands, water, metals) can now be controlled via the sequence view. But besides more space and a much cleaner interface, you may now see the binding site components of all loaded proteins.
    • The editor has been enhanced in two ways. Firstly, it is now possible to flip side chains of central atoms. Naturally the demand for this feature came from the need to flip stereo centers, but we did not limit it to just these. Click on the central atom and cycle through the viable options, the flip then requires just one more click. Secondly, we have added the more rare elements Boron, Silicon and Selenium and ordered the list of elements in the menu according to in the periodic table.
    • Normally users work on a particular computer with a particular setup (1 vs. 2 monitors, laptop vs. high-resolution big screen). So now you can arrange the layout of SeeSAR so that it best fits the geometry of your display hardware, such as the size of the different windows (whether all-in-one or docked out). SeeSAR stores these settings for you and next time it will open up any project using the same layout.
This new version of SeeSAR is full of usability enhancements plus a new, bulk docking feature.
  • multiple selections for bulk actions
    Frankly speaking we previously "abused" the favorite icon for making selections to initiate bulk actions. This itself undermined the point of being able to mark molecules as favorites. Now you may conveniently select multiple molecules using the new check box feature, and initiate bulk actions on the basis of this selection. For your convenience we also added a few functions to make working with these selections even more effective (un/check all, invert, ...). Just as for the favorites, shift + left mouse click works on the check boxes as a multiple un/check feature.
  • bulk docking
    A lot of users have been waiting for this feature! Now bulk docking can be carried out with just one click. Plus we have parallelized the docking calculation so that it now uses all processors on your computer, providing you with solutions swiftly — just as your hardware permits.
  • pharmacophore filter
    Now that you can run so many bulk actions, your solution list will grow by the minute. This made it just the right time to implement another filter option to help you keep track! Pharmacophore filters can now be defined using so-called sphere constraints. You can apply these pharmacophores at lightning speed to the molecule table and drill down solutions sets quickly and effectively with queries such as: Which molecules have an acceptor at this position? Filter out molecules that occupy this position! Give me all molecules with an aromatic moiety here!
  • other enhancements
    • A protein and ligand are sufficient to define the binding site in the vast majority of cases. The new shortcut behind the binding site button in the menu for a protein ligand now offers you a one-click binding site solution.
    • Partially hidden labels in 3D won't bother you anymore! Instead, the simple labels for showing distances, angles, and so on have been upgraded to the more advanced labels which we have always used for Hyde and more recently for displaying torsion information. These labels are movable (simply click and drag) and are always at the front. Plus, as a bonus feature, you may now also adjust the font size on the labels in the appearance settings menu in the toolbar.
A lot has changed in this new version of SeeSAR, justifying again a major update release. Our focus this time lay on the editor — essentially this has now evolved to become a full-blown "Designer"! Read on below to find out all the details. Among other things, an update to the torsion distribution database as well as an improved intra-molecular clash test can lead to changes in the affinity estimations using HYDE, which is why any existing affinity estimations will be re-set if you read in a project file from an older SeeSAR version.
  • Full integration of ReCore funtionality
    Until now, the core replacement facility in the editor only scratched the surface of the powers of the ReCore algorithm. Now, the joining and merging of fragments is also possible. In order to do this, the editor can be launched with multiple molecules at once — the 2D view in the editor supports this feature too. In addition, you can fine-tune results delivered by ReCore using pharmacophore filters.
  • Enhanced editing
    Many users have asked for a ring building feature in the editor to make adding entire rings at once possible. We have now added this feature as part of the Add Atoms submenu. The menu contains a selection of the most common rings and once you have added one to your molecule, you can then choose the most appropriate ring conformation by examining the choices in the 3D view. This feature means that large changes can quickly and readily be made to molecules and this in itself necessitates another new feature in the editor — namely that (if you have defined a binding site) new poses can be generated for the edited molecule based on the conformation of the molecule before editing. The positioning is carried out using the overlay of the MCS between the pre-edited and edited molecules as a basis.
  • Torsion distribution database update and display
    On the one hand, we have now integrated the latest update of the database of torsion angle distributions from the CSD, while on the other, it is now possible to view the torsion angle distribution for a particular rotatable bond. This is shown in bond labels analog to the display of HYDE score information in atom labels. A click on the eye icon in this label highlights the atoms involved in the particular torsion pattern that identifies the torsion distribution information in the database.
  • Other enhancements
    Several users have requested the possibility of saving their particular selection of favorites and any comments attached to a molecule via the SDF export. These are both now saved by default as SDF properties. Also, two filters can be added for numerical properties so that it is now possible to define both a lower and upper bound. Hydrogen bonds are now automatically hidden from view if the protein component of the hydrogen bond is hidden using the visualization settings in the toolbar. Last but not least, we have implemented a feature for measuring angles and torsions, besides distances.
  • Multiple protein alignment
    Since version 5.6 it has been possible to load and work with multiple proteins. So far this feature could only be utilized with pre-aligned structures. Now you can do the 3D alignment in SeeSAR itself. The alignment is based on and optimized according to the superposition of related active sites. Therefore, once you have selected a binding site, just one click is all that is needed to superpose all related binding sites at once. Note that the superposition is limited to highly homologous proteins (>90% sequence identity).
  • SeeSAR/StarDrop interface
    We have implemented a new function that greatly improves the interaction between the two software packages. Using the option in the molecule table toolbar, you may now transfer all (or the subset of favorite) molecules directly to StarDrop, which is launched automatically. This interface is supported in StarDrop starting with the recently released StarDrop version 6.4 and StarDrop now analogously supports launching and submitting data to SeeSAR. So it is in fact possible to transfer data back and forth and exploiting maximum synergy to make the best of both worlds. Note that this feature may require a few adjustments in your SeeSAR settings to become fully functional.
  • Shortcut to copy protein ligands
    Usually among the first tasks after loading proteins is to copy the related protein ligands to the molecules table for further processing (docking, editing, re-scaffolding, etc.). Especially with multiple proteins this turned out to be a quite cumbersome procedure. Therefore we have implemented a shortcut function in the toolbar of the proteins tab to copy all protein ligands at once to the molecules table. Note that this function will copy all ligands irrespective of their position in relation to the common binding site that is used in the context of the molecules table. So some of the copied ligands may lie well outside the common binding site.
The all new SeeSAR 6 provides you with a completely redesigned and now fully customizable GUI. You can choose between different bright and dark themes and GUI layouts so that you can optimally adapt SeeSAR for different use cases.
  • GUI design
    The new design is more streamlined and customizable. Instead of having 8 different kinds of buttons in different regions of the application, we now have just a main menu top left and a toolbar top right. The main menu changes depending on the mode of use (editing, site definition, ...), while the toolbar stays the same throughout. This way you are never overwhelmed with choices, but are only presented with options that you may need. Depending on you current use case, you may also want to change the overall layout (many molecules ⇒ tables to the left; many properties ⇒ tables below to make use of the whole width; 2 monitors ⇒ tables docked out) and/or the overall appearance (bright theme for presentations; dark theme for desktop work; we have also integrated a color blindness mode just in case).
  • Help
    In order to give you a jump start when you begin working with SeeSAR (both as a newcomer, as well as a seasoned user of the old GUI design), we have introduced an in-application help facility in this new version. First of all, upon starting the tool for the first time or after a long break in use, SeeSAR offers you a short introductory slide show, reminding you of a few basics that can make life a lot easier. But you can also now request help from within the application with a click on the lifesaver button. The help window then shows you – context dependent – explanations on the mode in which you are currently working or on the functions that you are trying to use so you can leave the help window open, consulting it when you need it. Of course you may also navigate between help pages in the help window and from there access online resources such as tutorial videos.
  • This new version of SeeSAR comprises another milestone in the evolution of our lightweight 3D modeling package, namely its ability to manage multiple protein structures simultaneously. Oftentimes, you may need to take account of multiple, related protein structures, perhaps either to identify the differences while aiming to achieve specificity, or — just the opposite — to find commonalities, such as when you are trying to ensure all variants of a protein will likely be inhibited. In this first implementation of the multi-protein feature, it is not yet possible to align protein structures but it is necessary to work with pre-aligned structures.
  • Loading multiple proteins
    Loading a protein does not now start a new project, but instead the new protein is simply added to a table of loaded proteins. In order to visualize the binding of ligands from the protein file, first select the protein of interest and then select one of the ligands listed in the table. As before, any of these bound ligands can be copied to the molecules table with a click on the molecule icon in the ligand table row.
  • Handling multiple proteins
    By default, the proteins chains are colored according to the same coloring scheme as before, with each chain in a different color. In the protein table you may set a unique color for a protein to ease identification that will be used for all components of that protein. If you edit a protein, the edited version of the protein will simply be appended to the table without overwriting the original. It is of course also possible to delete proteins from the table. Finally, you may choose the protein to be used for defining a common binding site from the table, just click the icon to start the binding site definition. Once a common binding site has been defined, a little binding site icon indicates which protein was used. Note that only this particular protein is used for the generation of poses, as well as for optimization and affinity estimation, i.e. the Hyde atom coloring on molecules is shown with respect to this protein.
  • Viewing multiple proteins
    Once a common binding site has been defined on one protein, the binding site itself is shown in greater detail. Now however, the regions of the other proteins in the vicinity of the common binding site are also shown in greater detail. This allows you to see the detail you need when seeking out differences or commonalities but the view may, however, become a little crowded. An enhanced menu under the protein visualization icon allows you to switch on and off different protein components (secondary structure, binding site amino acids, ligands, waters and metals) individually or as a group, and you may also change the visibility of entire proteins at once, all making handling of the view very flexible depending on your needs.
  • Other enhancements
    We have fixed some seldom occurring but still irritating issues with the 3D editor and also implemented the possibility to restrict the number of CPUs that SeeSAR may recruit for its computation on the command line. On windows, check --help to get an overview of all command line options. The option --thread-count allows you to limit the number of parallel compute threads as best suited. This feature is particularly useful if you run SeeSAR on a cluster which is controlled by a batch queuing system.
  • Shinier and speedier overall!
    Besides a load of novel features (cf. below) behind the scenes, SeeSAR has been given quite a bit of a boost! You will notice a speedier start, faster response times and - most noticeable of all - real time scrolling even if you have loaded thousands of molecules in your table. Note that several of the new features require an update of the underlying databases and therefore necessitate the re-calculation of Hyde scores from older SeeSAR project files!
  • 2D browsing featuring in-view molecule properties
    To further enhance the 2D browsing, we have added an illustration of the molecules' key properties in the form of a radar plot. A thumbnail of the plot is embedded in each of the 2D molecule pictures, providing a quick overview. it enlarges upon mouse-over and provides access to the configuration dialog. Add or remove property-axes, optionally fine-tune the scales and set 'desired' value ranges. A hit or miss of the latter is indicated by green or red dots on the corners of the color-coded characteristic shape of the molecule on the plot (the greener the better).
  • Detecting novel/unoccupied binding sites
    Now SeeSAR can search your protein for unoccupied pockets based on the world-renown DoGSite-Algorithm. You may then select these to become the binding site, within which to generate poses and calculate binding affinities for your molecules. The new binding site definition feature lets you either use a selected molecule from the table (based on a 6.5Å shell around it, as before) or will detect and visualize empty pockets for you to select instead.
  • Multiple reference molecules
    The reference molecule in SeeSAR always stays in view even when you select other entries from the molecule tables. Now, however, you are able to set - and keep in view - as many reference molecules as you like. Either set them individually - in the selected molecule menu (as before) - or mark several as favorites and set them all as references at once, via the new menu button below the table.
  • Multiple core replacements with just one click
    With the new multiple solutions button for ReCore in the molecule editor, brainstorming new scaffold ideas became yet easier. You can now generate 10 new alternative core replacements at once. The new molecules are saved directly to the table so that you can immediately see their estimated binding affinity and view all structures in 2D at a glance.
  • 2D molecule browsing - time to look at things from a different angle!
    While the molecule table offers great functionality for prioritizing compounds based on the data, it does not provide an overview of the molecules themselves. This release, however, sees the introduction of 2D molecule browsing. The table now offers two views - the one you already know and a 2D browser - flick between them using the switch below the table. Both views are always kept in sync so if you add a filter or sort etc. the 2D browser will show you the same result in the same order as the table. Also try expanding the table area to see how more molecules fit into the view.
  • Fantastic new 3D graphics featuresFantastic new 3D graphics features
    This release also brings with it some great new 3D graphics improvements. As much as we all like visualising the binding site surface, it lay often times in the way… The binding site surface can now be switched to transparent allowing you to see through it and therefore making the analysis of the binding site and molecules within much more comfortable. Also, the feeling of depth in the 3D view has been improved to help orientation - a so-called "fog effect" fades out the protein and molecules that are further away to bring the foreground more into focus.
  • Persistent amino acid labels and better view of reference
    So far, labels on binding site components unfortunately disappeared when browsing through different molecules in the table. Now amino acid, co-factor and water labels remain present if you change to a different molecule in the 3D view and even if you enter the molecule editor. The view of the reference compound has also been improved. For better visibility, the thickness of the bonds has been increased and instead of coloring the whole molecule in a uniform blue color, only the carbon atoms are colored blue so that hetero atoms can be distinguished more easily.
  • Think 2D in the 3D molecule editor!
    The molecule currently visible in 3D is also shown in a 2D representation below. Now in the editor the 2D representation is actually interactive - if you hover to highlight or click to select in 2D, the same will happen simultaneously in 3D and vice versa, giving you a quick and simple overview of the bonds and atoms currently selected ready for editing. This is especially useful for selecting a core fragment (e.g. lasso-style!) for the ReCore scaffold replacement feature.
  • Tweak your molecule conformation by hand in the editor
    Let's assume you made a major change to a molecule in the editor, for example by adding several atoms in a row, and the default positioning of the new fragment is not be optimal. Instead of finding yourself at a dead end, you can now adjust torsions in the editor: simply select a bond and then rotate either side of the bond to optimize the conformation within the context of the active site. While you rotate, the torsion coloring feature will guide you to avoid statistically unlikely states.
  • Key information from a PDB file at hand
    The PDB header contains a lot of unstructured / free text information. The items deemed of most importance are now extracted and shown in the lower part of the protein table tab. In a brief overview, you will find useful information such as the DOI, resolution, and a list of the components along with links to the primary data sources.
  • SeeSAR has a new, more flexible licensing scheme
    Previously, licenses for SeeSAR were issued with a fixed computer processor ID. Now server licenses are also available, meaning users can use SeeSAR from any computer that has access to the license server and are no longer restricted to working on the computer with the licensed processor ID.
  • Text label visibility improved
    You will no longer lose your text labels and 2D molecule representation if you change your background color to white (useful for presentations via LCD-projector)! If the chosen background color is brighter than a certain threshold, the color of the labels and 2D picture now switches automatically to maintain good contrast.
  • Discover the next ReCore features integrated into SeeSAR
    ReCore now takes the binding site into consideration when selecting new core fragments. Clashing as well as duplicate fragments are eliminated so that you will always see fresh ideas in the list. The new installation dialog offers you much more flexibility for installing a ReCore index file. It lets you download index packages from a dedicated website or load your own ReCore index file from disk. You trigger the installation either from the ReCore menu in the editor or via the Settings in the menu bar.
  • Simplify binding mode visualization
    Sometimes the 3D view of the binding mode can be quite busy. Especially if you are preparing a picture for publication or other reporting it is desirable to focus on the essential parts. Now you can fine tune which components of the binding site are shown in the 3D view with just a couple of clicks using the new sequence dialog in the visualization panel (top center). Note that this dialog is available only if a binding site has been selected for the molecule table. If you have calculated the estimated affinity already, you can show H-bonded residues with just one click.
  • Color coded protein surface
    This feature has been requested by many users and becomes reality with the new version. By default the surface is uni-colored but with a gradient according to the depth of the pocket. Alternatively you may select coloring by element or coloring by hydrophilicity based on the atom-specific logP values used for the Hyde affinity assessment (yellow means hydrophobic and blue the level of hydrophilicity).
  • Other improvements
    • Now also the 2D picture of the currently edited molecule is available.
    • Some use-cases require hiding or eliminating all unwanted molecules at once. To this end we enhanced the favorites filter to also filter the 'non-favorites'. So you can select all favorites => then hide them all => and delete all others.
    • Another minor annoyance was that the not-scored molecules always stayed in the way. Now if you filter to see only those compounds with an estimated affinity above a threshold we automatically filter out also all the not-scored compounds.
  • Now it's simple to rename your molecules
    Double-click on the molecule to type in a new name - this is particularly useful for renaming the results of molecule editing.
  • Access your files and recent downloads more easily with the centralized loader
  • Molecule annotation now only one click away
    The molecule annotation is now directly accessible with one click on the triangle mark to the left of the table rows. Mouse-over shows you your annotations while a click opens a small editor to edit them.
  • Core replacement preview
    Many of you will already know our award winning software ReCore. This release includes a sneak preview of the upcoming ReCore integration into SeeSAR. As this is only a preview release, you will need to carry out a few steps of preparation in order to discover its benefits:
    1. Download and save it to the folder or directory where SeeSAR is installed.
    2. Unzip the package into the same folder.
    In the editor, you can see the new ReCore button in the menu. Once you have selected a core fragment in your molecule - it must have 2, 3 or 4 non-ring bonds to other fragments - the button will become active and you can click it. One click shows you the best geometrically fitting fragment from the library, another click will show you the next and so on.
This new version brings together several new features designed to give you more control over how you interact with SeeSAR and to speed up browsing in 3D. This means that a new project version is necessary - but here you may find the new project recovery feature useful! Major new features include the new protein ligands, molecules and editor tables plus the editor itself has seen great improvements in user friendliness. Finally, don't miss the new editor feature for editing covalently bound molecules.
  • Neater molecule management with the new protein and molecules tabs
    The molecules table has now been given its own tab and is complemented by a new protein tab. This currently contains the protein ligands table showing the ligands loaded from your PDB file, while the table in the molecules tab is the molecules table you are already familiar with - having all the features previously found in SeeSAR such as filtering, calculating binding affinity with Hyde, pose generation etc. The editor has also been given its own fully interactive table to show the results of your last edits. Read more in the description of the new editor features below.
  • Edit, browse, and edit again - and even edit covalently bound ligands
    As promised we have now added more features for covalently bound ligands. In SeeSAR 5.0 you can edit covalently bounds ligands just like any other molecule or ligand. First add your ligand to the molecules table and then you can select it for editing. Once you are working in the editor, you can take the time to view the results of your edits complete with Hyde atom coloring in 3D. To go back to editing, simply click continue on the edit menu.
  • A new binding site definition for comparability and speed
    While the tables in the two tabs have the same look and feel, there are some slight differences. The protein ligands table shows you the binding affinity for all ligands in their binding sites as loaded from the PDB. However, to calculate the binding affinity or generate poses for molecules in the molecules table, you must first define a unique binding site. This binding site will be used for all molecules in the table, making the comparison of molecules that lie within the binding site more accurate - with the added bonus of greatly accelerating browsing in 3D. Currently the binding site can be defined really simply by choosing any molecule in either table as a starting point. The binding site then remains valid for all molecules in the molecules table until you decide to change your definition. The new binding site definition means that the estimated binding affinities calculated with the previous version of SeeSAR will now be incompatible with the new version and so they must be re-calculated. But SeeSAR can help you recover older projects - read on to find out more!
  • Recover projects saved with the previous SeeSAR version
    A major release includes major changes that mean older projects can no longer be loaded exactly as they were. However, SeeSAR now has new project recovery feature which will load as much data as possible from projects created with the previous version of SeeSAR. Any missing data can then be re-calculated with just a couple of clicks.
  • Control of Hyde affinity calculations handed to user
    Until now, SeeSAR automatically triggered the Hyde affinity calculations. This could be a long process, particularly when loading a large set of molecules from file, or after making an alteration in the Protein Definition dialog. Now, control is handed over to you the user to decide when the calculation should be triggered. This means large sets of molecules can now be loaded, analyzed and processed (e.g. filtering, calculating properties) before the intensive affinity calculations are run. You can trigger the affinity calculations just for a selection of molecules, for example, or even just for individual molecules in the Molecules table.
  • Enhanced filter features
    The collapse and expand buttons (formerly found below the Molecules table) have now been transformed into a filter feature. This feature groups together identical molecules (identified by their unique SMILES), leaving just the molecule with the best estimated affinity as the representative - which is what was previously described as 'collapsing' and was triggered using the collapse button. Also, previously the collapsing or grouping action was always applied before the filters - which was not made apparent with the buttons. Now, this filter is always the last applied. This is clear as the filter is always to the last one shown in the filter panel.
  • Other enhancements
    • On Windows, there was no output from SeeSAR when using the commandline interface - using the commandline on Windows was like flying blind! Just start 'seesar' on the commandline rather than 'seesar.exe' and the problem will be fixed. 'seesar --help' will give you more help getting started.
    • You can also export the protein ligands when using the commandline interface with the new option '--score-protein-ligands'. This is particularly useful if you need to analyse many protein-ligand complexes.
    • Covalently bound ligands are now optimized during the Hyde affinity calculation. This allows for a more reliable estimated affinity and is consistent with the treatment of all other molecules. Watch out for more covalent ligand features in following versions!
    • Finally, you may now load SD files of molecules into SeeSAR that contain many SD properties. SeeSAR will load the properties up to a maximum amount, whereas previously it was not able to load these files at all.
  • User-defined visualization settings
    Up until now, the 3D view settings were optimized for the current scenario, i.e. when you loaded a protein from file or project it was shown in overview, while after selecting a molecule, the view was focused in more detail on the binding site, ... This was quite comfortable - particularly for first-time users - but at the same time limited your freedom to choose your own viewing preferences. As of version 4.1, the user is back in charge. The optimized settings are still shown to start with but now you can choose to show or hide the following:
    • Hyde coloring for the selected molecule
    • torsion coloring for the selected molecule
    • whole protein
    • surface for the binding site of the selected molecule
    • unoccupied space in the binding site of the selected molecule
    • all waters in the binding site of the selected molecule

    The controls can be found in a panel above the 3D view on the main tool bar. There were previously some switches scattered about in different places in SeeSAR to control some of the these view settings - these have now disappeared having been replaced by the cleaner, less cluttered interface in the new panel.
  • Annotating molecules
    Many users have requested the option to add comments to specific molecules. We have now implemented this as a new feature that can be accessed via the notepad icon for the currently selected molecule in the table. A sticky note is opened where you can enter your comments for this molecule as free-form text. The annotations are saved along with the user name of the author. Molecules with annotations are indicated in the table by a yellow marker at the top left of the row in the molecule table. If you move the mouse over the marker, the annotation appears as a tool tip making it easy to quickly scan through all the notes in the table. These notes are saved to the project allowing you to keep your ideas and thoughts for later, or also to share them with others.
  • Enhanced project handling
    As of version 4.1, SeeSAR will now remind you to save your project if you have unsaved changes before you close SeeSAR or start a new project (either by choosing "New" or "Load" from the Project menu). You now also have the option to "Export" the raw data from your current project to a folder or directory of your choice. This will include the PDB file for the protein, all loaded molecules and any molecules you created using the editor.
This update of SeeSAR qualifies as major release 4, as several milestones have been achieved with it - namely the integration of the world-reknowned ADME property calculator from Optibrium™, the display of the protein surface in the 3D view, and an update of the Hyde scoring function. Collectively, these changes have made an update of the SeeSAR storage mechanism necessary, so unfortunately old project files cannot be loaded with this version. We recommend you save your molecules from old projects to file and re-read them with this new SeeSAR version. As an additional bonus feature we implemented the multi-selection of favorites with a simple [Shift] and click. Just try it out, it works as you would expect.
  • Optibrium
    As of version 4.0, SeeSAR is equipped with an interface that allows you to benefit from Optibrium's ADME property calculator from within SeeSAR. Any molecule loaded or edited is passed on to the property calculator, which itself applies multiple computational models to determine a variety of ADME properties. By default you'll see:
    • logP
    • logD @ pH7.4
    • logS (thermodynamic, intrinsic aqueous solubility)
    • logS @ pH7.4 (in phosphate buffered solution)
    • Blood-brain barrier penetration (log([blood]:[brain])
    • hERG inhibition (pIC50)
    • CYP2C9 affinity (pKi)
    • Human intestinal absorption (HIA) classification
    • Blood-brain barrier penetration classification
    • CYP2D6 affinity (pKi) classification
    • Plasma-protein binding classification
    • P-gp transport classification

    However, if you have additional models (within the Optibrium framework) you can add those too and have the respective values available at your fingertips. Note that the usage of this feature requires a separate license!
  • Protein surface
    The binding site of a protein is oftentimes quite complex making it easy to lose the sense of depth, space and tightness of fit. The protein surface of the binding site is now available to aid with orientation and can be toggled on and off very simply using a switch underneath the molecules table. This way, it is easy to switch between the surface view to find the orientation when you need to and the atom-only view at other times.
  • HYDE update
    Hyde is quite sensitive with regards to the numerical stability of the calculation, which we have significantly improved with this update. We also detected a small inaccuracy in the way the coverage of interactions is calculated which has now been corrected. Overall Hyde now has a higher hit rate with respect to the experimental data for high-quality structures and on average avoids overestimating the affinities, i.e. it now provides a more conservative estimate thereby reducing the rate of false positives.
  • Considering individual water molecules
    One of the particular strengths of the Hyde scoring function (and therefore SeeSAR) is its estimation of the effect of water. The whole concept of Hyde is based on the balance of desolvation and interaction. However, as always, the exception defines the rule: Namely, what is true on average for bulk water may be different for individual water molecules. For this reason, Hyde by default explicitly considers water molecules that are particularly tightly bound. Of course, the default may sometimes miss a water that is of particular interest, or take too many into account by including a water that might not be all that stable. Therefore, we have enhanced the Protein Definition dialog so that the user can now have the final say on which waters should be considered and which should be ignored.
  • Assessing covalently bound ligands
    Hyde is much liked for its visualization of the individual atom contributions to the overall binding affinity. This version also allows such visual assessment of covalently bound ligands. They are now listed in the Molecules table together with reversibly bound ligands and co-factors. As with all the other small molecules, a focussed view showing the individual atom contributions to binding is shown in 3D when the covalently bound ligand is selected in the table. We don't, however, provide an overall binding affinity for covalently bound ligands since it is meaningless in this context. Editing of covalently bound ligands is currently disabled but is planned as a feature for a later version.
  • Utilizing SeeSAR without a protein
    SeeSAR has grown from a single purpose affinity assessment tool to a multi purpose 3D structural viewer for compound design and prioritization. With this update it is now also possible to use all these nice features for 3D ligand-based projects. You may, for example, visually inspect small molecules alignments. You may filter a hit list by means of calculated and external properties...
  • Big data booster
    With version 3.0 we first equipped SeeSAR with database functionality. Version 3.2 comes with a load of performance enhancements that speed up the calculation by up to a factor of 5, now utilizing all available CPUs in your computer even more efficiently.
  • 3D graphics enhancement
    In this version we updated the graphics support and SeeSAR is now compatible with more graphics cards than ever before. Especially the compatibility with integrated graphics cards (the type most frequently found in laptop computers) - which used to be the major trouble makers - has been greatly improv
  • Working with "big data"
    With this update we lifted the limit of handling only a maximum of 5000 poses in SeeSAR. We know that a lot of people like to do their compound analysis and prioritization after virtual screening campaigns also with much bigger sets. It is not likely that you will look at more than a couple of hundred poses, however, since the filtering (see also below) is extremely efficient, it provides quite an attractive opportunity to load all your data (not just the top x) and do your prioritization with all properties at hand right here in SeeSAR.
  • Enhanced filtering
    Behind the scenes SeeSAR knows so much more about your compounds than what is displayed in the table. The basic stuff like no. of acceptors and donors, rotatable bonds, etc. to do the usual Lipinski-type filtering is of course available, but also more elaborate stuff like the number of hydrogen bonds formed or the number of torsions that lie outside the statistical "norm". All of these are now available for filtering to help you optimally trim down your data to find the really interesting part.
  • Older project files invalid
    Please NOTE: SeeSAR project files from older versions are incompatible and cannot be loaded. By default SeeSAR puts a new version in a separate location. So your old version should still be there. If you happen to have lost the old version, please contact us.
This update of SeeSAR qualifies as major release 3, since it covers two milestones in its development. So far every SeeSAR session has started from scratch. The only way to retain molecules was to save them to file and re-load them again in a subsequent session. Needless to say that loading meant recalculating all Hyde scores again...
  • Project files
    Starting with Version 3.0, SeeSAR allows you to store all session data in a project file. This includes the protein, ligands loaded from file and new (edited) ligands. Resuming your work on a project is now as easy as double-clicking on the project file. As a result, everything just got a hell of a lot faster! Whilst calculating Hyde-scores for say 1000 compounds took around half an hour (depending on your hardware), loading the same information from a project file now takes only a few seconds. Note that you can also generate a project file on the command line, allowing you to outsource the calculation of Hyde-scores to a different machine. This enhancement is also a great way to exchange data and ideas with a colleague! Simply store your SeeSAR session as a project file in a commonly accessible location (e.g. a network drive). Your colleague can take a look with just a double-click.
  • Hyde update
    Hyde is quite sensitive with regards to the precise geometry of a binding pose. Even the tiniest difference in a pose can distort an anyway stretched hydrogen bond just so much that it is not recognized anymore - thereby leaving you with a huge desolvation penalty for such atoms, without the gain from the H-bond. This 'sharpness' of Hyde is its greatest strength (for example by highlighting real activity cliffs), but also its greatest weakness (especially if the structure has flaws or is of low resolution). In order to minimize such troubles, we optimize each pose before the Hyde affinity assessment. We improved this optimization significantly. It is now fully flexible and with sharper clash criteria, making it suitable for docked poses as well as edited compounds. All of this as efficient as before, just perfect for interactive use.
  • Solution filter
    Finding interesting solutions in larger sets of compounds has just become much easier in SeeSAR. Compounds can now be filtered based on any available property - allowing you to easily trim down the compound set to the most interesting fraction.
    As before, you can browse through and sort the remaining table entries to further refine your selection. Properties can be those generated by SeeSAR (such as the Hyde affinity assessment, the torsional strain, TPSA, logP, ...) or alternatively properties loaded from an SD file.
  • Joined poses
    We have joined the ligands found in the protein structure, compounds loaded from file and compounds newly generated within the SeeSAR editor into one 'super' table and now provide quick-links to the previous view of only those from a certain origin. This allows you to see in one table the bound ligand as a reference, the project compounds and your last round of designs. You can then select your favorites from the entire table and export these (for example for an upcoming team meeting).
  • Defining the protein
    SeeSAR decomposes the contents of a PDB file into chains, small molecules, waters and ions. Until now, users had to accept SeeSAR's default assignments, which is fine in the majority of cases. However, there is no rule without exception, e.g., the peptide inhibitor which is mistaken as a short chain, the small molecule which is actually a co-factor, or the solvent molecule that should be ignored. With this update, SeeSAR allows you to change these default assignments to better handle these exceptional cases, allowing you to categorize a short chain as a bound ligand, or re-assign a co-factor as a permanent part of the protein. You can also eliminate protein elements altogether.
  • SMILES, PDB and MOL file support
    We equipped SeeSAR with additional molecule readers that broaden the scope of the application. Aside from standard 3D molecule file formats (SDF and mol2), SeeSAR now supports 1D and 2D file formats as well as reading small molecules from PDB format. If no 3D coordinates are given, SeeSAR will calculate a clash-free, low energy conformation on the fly: with the SeeSAR positioning function you can then place such input molecules in the active site of interest. Amongst other things, this feature facilitates the importing of molecules straight from your favourite chemical drawing program and assessing such structures in in the context of your protein of interest.
This update of SeeSAR qualifies as a major release, since it covers a milestone in its development. So far SeeSAR was able to assess given poses of small molecules in a protein structure. Starting with release 2.0 SeeSAR can also generate poses. Also note that the Hyde affinity assessment behind the scenes has been further improved by a variety of fixes and small changes for the benefit of more stability of the calculations. These changes will have an effect on the computed scores. If you rely on the scores resulting from a specific version of the tool, we recommend you to keep such older versions of the tool in an archive.
  • Pose generation
    SeeSAR assesses the binding affinity based on the given position of the ligand in the active site. New in major release number 2 is the introduction of ligand pose generation directly within SeeSAR. So now you can draw and save a molecule in 2D, load it and have SeeSAR predict both binding poses and the related affinity for those poses. Similarly, if you make a substantial modification to the ligand in the editor, you can now validate the original position by generating new binding poses followed by the affinity assessment.
  • Ring conformation sampling
    Significant conformational changes occasionally occurred when ring atoms were modified, reducing confidence in the Hyde estimated binding affinity. We have overcome this by implementing a conformational sampling of ring systems to identify the closest of all energetically favorable ring-conformations.
  • Stay focused
    Sometimes, the 'big picture' can get lost while browsing and inspecting poses in 3D - users can now reset to a standard orientation by hitting 'Space' on the keyboard or with a click on the center view button in the utilities area (lower right corner in the 3D view).
  • Improved editing
    One key functionality that was missing from our molecule editor was the ability to manually set atomic charges. We trusted the compute engine underneath (ProToss) to identify the most likely state automatically when optimizing the overall hydrogen bonding network. However, there are always exceptional cases that prove the rule. Now the user has the final say in this by being able to set the charge for individual atoms. Also, within the scope of the application the user setting won't be overwritten. Hotkeys '+' and '-' make these changes happen really quickly.
  • Improved table handling
    • 2D-depiction: a picture says a thousand words... To quickly eyeball a compound of interest in a SeeSAR table we implemented a feature to show the structure upon mouse-over.
    • Picomolar affinity: one of the main applications of SeeSAR is in lead optimization where it is not uncommon to work with extremely potent molecules. These are now better accommodated by an extension of the estimated affinities into the picomolar range.
    • Pose-specific functions close by: your mouse used to travel a fairly long distance from selecting a compound to the bottom of table to either edit, delete or keep a table entry in view. Now, these buttons appear just underneath the selected row.
    • Show/hide multiple table columns: The context menu to add and remove table headers now stays in view for multiple selections and disappears gracefully if you click on anything else in the application.
  • More convenient structure editing
    In order to make structure editing an even more convenient, swift and fun process, we have added a few new features:
    • Hotkeys: simply select an atom, then type N to change it to a nitrogen. Obviously this "element change" shortcut works for all one-letter types (C, O, N, S, P, I).
    • Context-menus: simply right-click an atom (or bond) to get the all options to add a new atom (or change the bond type) right there.
    • Draw bonds: simply click & hold on an atom, then drag to a second atom to connect the two with a new bond.
  • Improved table handling
    After a virtual screen or docking run, many users will load multiple poses of each of their molecules and then interactively undertake the crucial steps of visual validation and selection. We improved SeeSAR in this regard with two new features.
    1. For a better overview, you can now collapse all poses of one molecule to a single, representative table entry. This will be the best Hyde-scoring pose. Obviously you can also reverse this process and expand the table to show all the poses.
    2. As you go through the table you can mark the poses as favorites that you would like to keep. Following this, you can then choose to export only your favorites.
  • Stereo Graphics
    One of the top features on the wish list was stereo support for polarization hardware. So here it is! To activate stereo mode simply open the settings dialog and check the box for stereo view under Display. You can make adjustments for your eye distance using the slider too.
  • UX Further Improved
    We have taken time to add some more enhanced user experience (UX) features. The main features are:
    • Re-position labels: Labels (activate this feature using the label icon in the utilities box, bottom right) provide useful information when you click on objects in the 3D view. Now you may drag labels to a different location. This is handy for preparing images to include in presentations and for de-cluttering your view.
    • Browse ligand table contents without leaving the 3D view: Jump from pose to pose with just a keystroke. Simply use the up/down arrow keys on your keyboard. You can even use the delete key, but watch out as there is no undo yet!
  • Screenshots made easy
    A neat new convenience feature has been added to this version. Simply click on the camera icon in the utilities box (bottom right) and save your picture.
  • 2D visualization of selected ligands
    When things get complicated in 3D, it may help to drop a dimension: You can now check the 2D formula of a ligand at the bottom left - Prerequisite: the ligand must have been selected with a click on the respective table line. If you would still like to exploit the full 3D view, just hover over the 2D sketch and a collapse icon will appear for your convenience. Please note that during editing, the 2D picture will only be updated upon leaving the editor (shortcut: just press ESC to leave the editor).
  • Work with your own SD properties
    Sort, check, visually correlate your own information stored in the SD files you use: Upon loading ligands via the menu entry (the 'L' icon in the upper left), we parse your information and you can add it to the properties table on demand. Additional SD properties are added by selecting them from the property drop-down icon at the far right of the table header. A mouse-over on the table column headers will display your property's full name. So, if you had, for example, your own favorite solubility predictor write its prediction into the SD file, you will now have the value ready to use in the table.
  • Web settings to comply with corporate environment
    Your corporate security rules may force you to access the internet through a dedicated computer. You can now specify a proxy to make sure SeeSAR remains fully operational. Please note that the information about the latest updates (displayed when you click on Updates in the Information menu - '?' icon) is obtained from our webpage. If you can't access this information, this may be a hint that you need to change your proxy access settings.
  • See torsions color-coded by statistical relevance
    We now color rotatable bonds in a simple traffic light scheme to show you whether your torsion angles are similar to those observed in crystals or not. Please note that this is not an energetic statement but rather a statistical one. You can switch between this view and Hyde coloring by using the toggle switch at the bottom left of the table. The colors have the following meaning: red = seldom, yellow = occasional, green = frequent
  • Show receptor atoms contributing to a Hyde score
    In SeeSAR, the contributions of receptor atoms are projected onto the ligand atoms, i.e. a red ligand atom can be red because a protein atom is 'unhappy'. To find out which receptor atoms contribute to the ligand atom Hyde score, switch on the label for the respective ligand atom using the label functionality in the utilities area (lower right corner in the 3D view), and click on the eye icon to highlight the contributing receptor atoms.
  • Quick, convenient distance measurements
    To speed up measuring several distances from one given atom, you can now view distances with mouseover. Switch on the distance measurement mode using the utilities area (lower right corner in the 3D view), select an atom, and distances to other atoms will appear upon mouseover. If you click on a second atom, the distance measurement will be kept visible permanently.
  • Lipophilic Ligand Efficiency (LLE) - a new property
    We have implemented an approximate LLE as an additional guideline property in the tables. The orientation of the thumb symbol indicates whether the LLE is great, good, fair, mediocre, or poor. The calculation is based on the Hyde estimated binding affinity and atomic logP values. The traditional Ligand Efficiency (LE) is still available; you can toggle both properties on/off (just as for all other properties) by using the selection tool at the far right of the table header.
  • File dialogs now remember your last location
    When you load protein or ligand data, your last chosen directories will be remembered.
  • License expiration alert
    5 days before your license runs out, an alert dialog will appear when you start SeeSAR.
  • New version alert
    When a new version becomes available, SeeSAR will show an alert on the information symbol in the toolbar above right. Click the 'Updates' icon in the information menu to see the new version details.
  • Conformers color-coded according to crystal torsions
    For every molecule in a table, a traffic light style flag is now shown. This gives you a feeling for your ligand torsional conformation based on a comparison of the torsions in your molecule with respect to those observed in crystals. Please note that this is not based on energies but on statistical significance. In other words: The more frequently your torsions match those observed in crystals, the more likely the flag will say 'OK.' This is what the color-coding means:
    • green = most torsions are observed frequently,
    • yellow = some torsions are seldom or occasionally observed,
    • red = several torsions are only seldom observed.
  • Visualize the 'explorable volume' of your complex
    We implemented a swift visualization of where the tightness of fit can be improved, or where you can avoid the horror vacui in your binding site: While you are in 3D edit mode, white 'fog' will indicate empty space in the binding interface.
  • Multi-file loading
    You can now load multiple ligand input files at once by performing a multi-selection using the Ctrl/Shift/Apple keys.
  • Unified labeling
    Instead of separate labels for Hyde score, atom names, etc., we have now consolidated all this information in a single label per atom. To activate the label, use the label icon in the utilities area in the lower right corner, and click on an atom.
  • Drag and drop license files
    License files (*.lic) received from us can be drag and dropped into a dialog opened from the information menu in the toolbar: Information >> License. This way, licensing SeeSAR becomes child's play!