Glossary

Speaking the Language of BioSolveIT

Every field needs its own language to enable clear communication, and BioSolveIT is no different. That’s why we’ve gathered the most important vocabulary about our world and drug discovery in general in one place, to provide an easy-to-understand overview.

 

 

 

Glossary of BioSolveIT Terms
Term Definition
ADME properties Absorption, Distribution, Metabolism, Excretion — Pharmacokinetic parameters that describe how a drug is processed by the body. Can be predicted by the optional Optibrium module in SeeSAR and infiniSee/xREAL.
AMBRosia A Chemical Space by Ambinter. Read more about AMBrosia here.
Analog Hunter A Search Mode within infiniSee that retrieves close analogs based on molecular fingerprint similarity, using the SpaceLight algorithm.
Anchoring Step The initial phase in Chemical Space Docking® where pre-processed building blocks (synthons) are docked into the target’s binding site.
Bemis-Murcko Scaffold A common chemical structure or core motif found in a set of molecules, used to classify molecular diversity.
Binding Site Mode A Mode in SeeSAR used to detect potential binding sites for a ligand, expand them, or find empty pockets in a protein.
Building Blocks Small molecular fragments that can be combined through chemical reactions to generate a vast number of compounds within a Chemical Space.
CHEMriya A Chemical Space by OTAVA. Read more about CHEMriya here.
Chemical Space A theoretical or virtual collection of all possible or synthesizable chemical compounds, often characterized by building blocks and reaction rules rather than an explicit list. Can contain trillions or more of entries. Read more following this link.
Chemical Space Docking® (C‑S‑D) BioSolveIT’s next-generation structure-based virtual screening method for efficiently mining promising hit candidates from ultra-large Chemical Spaces. Read more following this link.
CoLibri A command-line tool used to create combinatorial Chemical Spaces from building blocks and formalized reaction definitions. Read more following this link.
Combinatorial Chemistry A method of synthesizing a large number of chemical compounds simultaneously by combining different sets of reagents in all possible combinations.
Combinatorial Chemical Space A Chemical Space generated using combinatorial chemistry, where compounds are formed on-the-fly from building blocks and reaction rules, rather than being explicitly listed. See also “Chemical Space”
Conformator A command-line tool by BioSolveIT used to generate single 3D conformations or ensembles of conformers for input molecules. Read more following this link.
Connected Substructure Fingerprints (CSFPs) A type of molecular fingerprint, including variants like fCSFP, tCSFP, and iCSFP, designed to mine relevant chemistry from combinatorial Chemical Spaces by capturing more and smaller features than ECFP. Available for the SpaceLight algorithm.
Covalent Docking A docking method in FlexX and SeeSAR that models the formation of a covalent bond between a ligand’s warhead and a protein residue.
“Crystal Structure First” Approach A strategy in fragment-based drug discovery that prioritizes crystallographically confirmed fragment hits with validated binding modes as starting points for fragment evolution, rather than relying solely on affinity metrics.
Custom Libraries Project-specific molecule datasets generated from Chemical Spaces. Due to the vast size of Chemical Spaces, they can yield enough relevant compounds to create diverse, tailored libraries for various applications, including machine learning model training or specific kinase projects.
Desolvation One of the major driving forces of ligand binding in aqueous solution, along with interactions. HYDE, a scoring function, is “desolvation-aware” and calculates realistic free energies of binding based on the difference between the bound and unbound states.
Docking Mode A Mode in SeeSAR for predicting binding modes of ligands, screening libraries for actives, and evaluating results. Supports standard, template-based, and covalent docking.
Docking Score A numerical value used in virtual screening that reflects the interaction complementarity and predicted affinity between a target structure and a ligand.
DogSiteScorer An algorithm implemented in SeeSAR that helps to define potential binding sites in a target protein based on predicted druggability. It can suggest relevant residues and assess the properties of the binding sites, such as cavity size and lipophilicity.
Drug-Like Properties Characteristics of compounds that indicate their suitability as potential orally active drugs in humans. These properties are often assessed using rules like Lipinski’s Rule of Five (Ro5). Chemical Spaces aim to provide a high number of compounds with drug-like properties.
Enumerated Library A traditional compound collection where each entry is explicitly listed, contrasting with combinatorial Chemical Spaces where compounds are generated on demand.
eXplore A large make-on-demand Chemical Space by eMolecules known for providing accessible compounds for drug discovery.
Extension Step A phase in Chemical Space Docking® where selected “anchors” (initial synthons) are grown into larger, more complete drug candidates by adding further building blocks.
Extended‑Connectivity Fingerprint (ECFP) A widely used type of molecular fingerprint (e.g., ECFP4) that describes a molecule’s structural features and connectivity as a binary code, enabling similarity comparisons. Available for the SpaceLight algorithm.
FastGrow A BioSolveIT tool for structure-based fragment growing and pocket exploration, used to attach fragments or building blocks to a core molecule in a protein’s binding site. Also available in SeeSAR‘s Inspirator Mode. Read more following this link.
Feature Trees (FTrees) A BioSolveIT algorithm and command-line tool for fuzzy pharmacophore similarity searching across chemical spaces, representing molecules as trees of molecular substructures and their connectivity. Used in infiniSee‘s Scaffold Hopper. Read more following this link.
FlexS A command-line tool for 3D alignment and superposition of molecules, often used in ligand-based virtual screening when the target structure is unknown. This algorithm is also applied in SeeSAR‘s Similarity Scanner (Mode). Read more following this link.
FlexX A BioSolveIT tool for flexible protein-ligand docking at the command line, supporting standard, template-based, and covalent docking. This algorithm is also applied in SeeSAR‘s Docking Mode. Read more following this link.
Fragment-Based Drug Discovery (FBDD) A drug discovery approach that starts with small, less complex compounds (fragments) as initial hits, which are then optimized to drug-size candidates.
Fragment Growing A common strategy in Fragment-Based Drug Design (FBDD) where an initial fragment hit is extended by adding functionalities into unoccupied areas of the binding pocket. This aims to increase the compound’s potency and affinity. FastGrow is a tool specifically designed for this purpose.
Fragment Linking A FBDD strategy that involves connecting two or more distinct fragments that bind in separate sites within the target protein. This allows for the design of new compounds that combine the desirable features of multiple fragments, enhancing their binding affinity. Fragment linking can be performed in SeeSAR‘s Inspirator Mode.
Fragment Merging A FBDD strategy where two fragments with overlapping moieties or specific molecular interactions are combined to create a unified chemical entity, often leading to synergistic improvements in potency. Fragment merging can be performed in SeeSAR‘s Inspirator Mode.
Fragments Small, low molecular weight compounds (typically <300 Da, Rule-of-Three compliant) used as starting points in FBDD.
Freedom Space A Chemical Space by Chemspace. Read more about the Freedom Space here.
Fuzzy Similarity A type of similarity search that allows for less strict matches between molecular structures, enabling the discovery of chemically related compounds that might be missed by methods relying on exact connectivity or atom types. FTrees uses a fuzzy pharmacophore similarity search. FlexX‘s MCS algorithm also incorporates “fuzziness” for template docking.
GalaXi A Chemical Space by WuXi.
HPSee HPSee is BioSolveIT’s scalable workflow infrastructure and virtual screening environment, enabling efficient handling of large compound collections and supporting C‑S‑D calculations on external hardware.
HTS (High‑Throughput Screening) A conventional method in drug discovery for rapidly testing a large number of compounds for biological activity.
HYDE BioSolveIT’s desolvation-aware scoring function and command-line tool for predicting ligand binding affinity and identifying affinity problems in protein-ligand complexes. Provides visual, per-atom contributions in SeeSAR. Read more following this link.
infiniSee infiniSee is BioSolveIT’s Chemical Space navigation platform with a graphical user interface, used to retrieve relevant chemistry from ultra-large Chemical Spaces based on similarity to a query compound.
infiniSee xREAL infiniSee xREAL is a specialized version of infiniSee that exclusively screens Enamine’s xREAL Space, the largest catalog of drug-like compounds.
Inspirator Mode A mode in SeeSAR that offers suggestions for compound modifications, including scaffold replacement, ligand growing, and substituent sampling.
Knowledge Space An ideation-focused chemical space available from BioSolveIT.
Lead-Like Properties Characteristics of compounds that make them suitable starting points for lead optimization. These include criteria such as a molecular weight typically between 200–400, logP less than 4, and a lower number of rotatable bonds and hydrogen bond donors/acceptors compared to drug-like compounds.
Lead Optimization The process of iteratively modifying a hit compound to improve its potency, selectivity, and ADME properties.
Ligand Efficiency (LE) A metric used to assess the binding efficiency of a ligand, calculated based on its binding affinity and molecular weight.
Ligand-Based Drug Design (LBDD) Drug design approach that relies on known binders to propose potential new binders, without requiring the target’s 3D structure.
Linker Constraint A feature in Chemical Space Docking® that guides pose generation by modeling a chemically inert phantom atom (like an ethyl group) to sample clashes and define extension direction.
Lipinski’s Rule of Five (Ro5) A set of rules (MW ≤ 500, logP ≤ 5, H-bond donors ≤ 5, H-bond acceptors ≤ 10) used to predict whether a chemical compound has properties that would make it orally active in humans.
Lipophilic Ligand Efficiency (LLE) A metric that combines binding affinity with lipophilicity, useful for assessing the quality of fragment binders.
Maximum Common Substructure (MCS) Search A cheminformatics approach involving finding the largest common chemical motif shared between a query molecule and compounds in a database. Applied in the SpaceMACS algorithm and infiniSee‘s Motif Matcher Mode.
MedChemesis A ligand mutation tool integrated into SeeSAR‘s Inspirator Mode. It applies a library of approximately 290 commonly used medicinal chemistry transformations to a query compound to generate closely related analogs, helping medicinal chemists explore potential improvements.
Medicinal Chemistry Transformations Common modifications made by medicinal chemists to compounds to improve their properties, such as adding functional groups, exchanging atoms, or converting motifs into bioisosteric counterparts.
Molecule Editor Mode A Mode in SeeSAR allowing users to modify molecules in 2D or 3D on-the-fly.
Motif Matcher A feature within infiniSee that performs substructure matching, including maximum common substructure (MCS) searches and exact substructure mining, using the SpaceMACS algorithm.
New Chemical Entities (NCEs) Molecules that contain structural motifs or moieties that have not previously been reported in approved drugs or clinical trial candidates. NCEs are highly sought after as they represent potential first-in-class therapeutics and offer significant intellectual property value.
Orthogonal Methods Refers to different computational search methods or algorithms that explore distinct aspects of chemical similarity or chemical space, thus complementing each other. For example, FTrees (pharmacophore-based), SpaceLight (fingerprint-based), and SpaceMACS (substructure-based) are described as orthogonal methods for chemical space exploration.
Pharmacophore Constraints User-defined criteria (e.g., hydrogen bond donors/acceptors, hydrophobic contacts) applied during docking or screening to guide the search for compounds that meet specific interaction requirements.
PDB (Protein Data Bank) A global archive of 3D biological macromolecular structural data.
Protein Editor Mode A Mode in SeeSAR allowing users to modify proteins, including exploring rotamers, introducing mutations, and customizing side chains.
PROTAC Bifunctional molecules designed to induce targeted protein degradation.
REAL Space A large, make-on-demand Chemical Space by Enamine, used as a source for virtual screening.
ReCore An algorithm used in SeeSAR‘s Inspirator Mode for 3D scaffold replacement, searching databases for fragments that match specified 3D vectors.
R‑group Search A type of substructure search (in SpaceMACS) that identifies compounds containing a specific motif with additional substituents at defined positions.
Rule of Three Guidelines for fragment-likeness (≤3 H-bond donors, ≤3 H-bond acceptors, ≤3 rotatable bonds, MW <300, logP ≤3).
SAR (Structure‑Activity Relationship) The relationship between a chemical structure and its biological activity.
SAR‑by‑Space An efficient method for establishing SARs by exploring the vast number of commercially available analogs within Chemical Spaces.
Scaffold Hopper A Search Mode within infiniSee that performs fuzzy pharmacophore searches to find distant, non-obvious analogs using the FTrees algorithm.
SeeSAR SeeSAR is BioSolveIT’s intuitive, visual 3D drug design platform, integrating various tools for drug discovery, including docking, fragment-based design, and Chemical Space Docking®.
Similarity Scanner A Mode in SeeSAR that performs ligand-based virtual screening by aligning molecules with a template structure based on interaction features, volume, and shape (using the FlexS algorithm).
SMARTS A language used to describe molecular patterns, used for substructure searches and defining reaction rules.
SMILES A notation for representing molecular structures as a line of text.
SpaceLight A command-line tool and algorithm used in infiniSee‘s Analog Hunter for fast, fingerprint-based similarity searching in chemical spaces to find close analogs.
SpaceMACS A command-line tool and algorithm used in infiniSee‘s Motif Matcher for maximum common substructure (MCS) and exact substructure searches in Chemical Spaces.
Standard Virtual Screening Traditional virtual screening that processes pre-enumerated compound libraries, often by brute-force docking, as opposed to generating compounds on-the-fly from a Chemical Space.
Structure‑Based Drug Design (SBDD) Drug discovery approach that relies on the 3D structure of the target protein to design and optimize ligands.
Synthetic Accessibility The ease with which a chemical compound can be practically synthesized in a laboratory. Chemical Spaces are designed such that the compounds generated “on-the-fly” are synthetically accessible, often in one or two steps, allowing them to be purchased or synthesized in-house.
Synthons Conceptual building blocks used in the synthon strategy of Chemical Space Docking®, representing the smallest units containing an extension vector.
Template Docking A docking method in FlexX and SeeSAR‘s Docking Mode where a common core of an input ligand is superposed onto a known conformation of a template ligand, preserving that conformation during pose generation.
Torsional Strain Energy associated with deviations from ideal torsion angles in a molecule, assessed by HYDE to evaluate pose quality.
Virtual Screening (VS) Computational methods used to identify potential drug candidates by searching large databases of compounds for those most likely to bind to a target.
Warhead A functional group in a covalent drug that forms a covalent bond with a target protein residue.
xREAL Space Enamine‘s most extensive catalog accessible via infiniSee xREAL. It vastly outperforms the well-known REAL Space.
YASARA An optional third-party integration in SeeSAR that allows users to perform energy minimization to optimize target structures and models.