Chemical Space Docking®

Chemical Space Docking® Chemical Space Docking® is BioSolveIT's response to structure-based exploration of more than billions of compounds. The novel approach mines the best drug candidates with exceptional efficiency and sophistication. Learn more Unlocking the molecular universe Advantages Get started

Extracting Relevant Chemistry from Molecular Macrocosm

Chemical Space Docking® grants you access to ultra-vast Chemical Spaces encompassing billions or even more molecules.

The interactive workflow enables users to engage with the results at every stage, effectively guiding the project towards success. Results retrieved are synthetically accessible, and in the case of our partners' Chemical Spaces, also commercially available.

The Concept of Chemical Space Docking®

The concept of Chemical Space Docking® is an efficient, structure-based exploration of ultra-vast compound collection.
Rather than employing brute-force docking of over billions of compounds, a method that could take months to years to finish, Chemical Space Docking® focuses only on promising and relevant chemistry to save computation time and resources. Poorly performing drug candidates are rejected at the beginning of the workflow, putting the focus on only the interesting options.

Starting from the smallest feature that create a drug candidate, namely the building blocks, full-fledged compounds are combinatorially assembled within the binding site. Using defined chemical reaction rules, the resulting compounds are synthetically accessible and are available for purchase through our affiliated compound vendors.

Three Flavors of Chemical Space Docking®

C-S-D GUI icon

GUI

SeeSAR & HPSee

Run C-S-D interactively from the SeeSAR interface. Define the binding site, set pharmacophore constraints, and inspect and pick poses visually at every stage, while HPSee orchestrates the remote compute in the background.

Best for: Medicinal and computational chemists who want to stay hands-on and in full visual control.

C-S-D API icon

API

HPSee & Python (e.g., Jupyter)

Drive C-S-D from Python and fold it into your own pipelines. Start workflows and pull results through the HPSee API, combine them with your own scripts and libraries, while HPSee still orchestrates the remote compute.

Best for: Computational scientists who want automation without managing the full infrastructure.

C-S-D CLI icon

CLI

Command Line Tools

Run C-S-D from the command line using standalone executables. The tools run natively on your own cluster, workstations, or HPC scheduler, so you keep full control over orchestration and parallelization, with no HPSee required.

Best for: Advanced teams that run their own infrastructure and want C-S-D in existing pipelines.

Explore the deployment options Overview Deployment Options [PDF]

The Science Behind the Innovation

Instead of relying on resource-intensive brute force docking of compounds typically employed in conventional virtual screening, Chemical Space Docking® prioritizes the selection of the most promising candidates that effectively extend into the binding site.

Bigger is better for virtual screening. Only a fraction of brute-force resources is required. C-S-D retrieves novel chemotypes. SAR-by-catalog enables rapid follow-up. Better scoring candidates emerge.

Fine-Tuned Methodology

  • Docks real synthons directly.
  • Chemically inert dummy-atom extension vector.
  • Avoids bias from preselected minimal products.
  • Probes the target surface around the synthon.
  • Detects clashes before extension.
  • Avoids generating clash-prone poses.
  • Optional use of co-crystalized ligand or predicted poses.
  • Guides anchoring and pose generation.
  • Accelerates sampling of relevant binding modes.

Advantages of Chemical Space Docking®

Save Time — A Lot of It!

Docking of billions of compounds can take up months to years to complete on standard hardware. Chemical Space Docking® does the same in days — only a fraction of time!

Interactive Workflow

You know your target best. Use your knowledge to guide your screening by applying pharmacophore constraints. Furthermore, SeeSAR helps you to cherry-pick the best candidates for follow-up by providing you with visual support to understand your target-ligand complex.

Several Chemical Spaces Available

Collaborations with our compound vendor partners have led to a variety of commercial Chemical Spaces. Each one of them comes with unique building blocks and in-house reactions that lead to unique compounds.

Sophisticated User Interface

SeeSAR was designed to be fast, visual AND easy. Every stage of the Chemical Space Docking® workflow is easy to understand and to operate. With this, computationally-unexperienced medicinal chemists and even drug discovery beginners can delve into ultra-vast compound collections for novel IP and promising results.

Runs on Standard Hardware

No need for extensive computational resources. SeeSAR and Chemical Space Docking® are easy to set up, making them accessible even to smaller companies and research groups.

Retrieves Molecular Novelty

Chemical Space Docking® was shown to mine novel and potent chemotypes from Chemical Spaces. It can retrieve diverse chemistry complementing different subpockets of the target, fueling your pipeline with a variety of scaffolds.

Advantages of Chemical Space Docking®

Random Docking Wastes Time — Be Smarter

It has been demonstrated that sampling random molecules leads to abysmal docking scores for over 95% of the ligands in the majority of cases.
Essentially, this implies that in conventional virtual high-throughput screening a significant portion of computations is allocated to fundamentally unsuitable candidates.

In comparison to brute-force docking methods, Chemical Space Docking® significantly accelerates the process, efficiently enriching a diverse set of high-scoring compounds in a fraction of the time.
Boldly said, you discover more and superior compounds at a faster pace.

Harvest Your Full Potential

You can also create your own, bespoke Chemical Space using in-house building blocks and chemical reactions to define hunting grounds only you have access to. It does not require much to reach billions or even more due to the combinatorial nature of the method.
The beauty of the approach will provide you with compounds that you can easily synthesize in one or two steps while browsing through ultra-vast compound numbers.
This can enormously accelerate your in-house projects while maximizing the scope of your intellectual property.

We also offer the generation of your own Chemical Space and expansion of a Chemical Space with individual reactions and building blocks as a service.

Which Flavor Fits Your Workflow?

C-S-D GUI icon

GUI
SeeSAR & HPSee

C-S-D API icon

API
HPSee & Python (e.g., Jupyter)

C-S-D CLI icon

CLI
Command Line Tools
In a nutshell
Run C-S-D interactively from the SeeSAR interface. HPSee orchestrates the remote compute in the background. Automate C-S-D workflows in Python while HPSee handles job distribution and compute resources. Run the individual C-S-D tools directly and manage orchestration, parallelization, and infrastructure yourself.
Where the compute runs
HPSee, deployed on a single machine (Compose Mode), across several machines (Swarm Mode), or on AWS. HPSee, deployed on a single machine (Compose Mode), across several machines (Swarm Mode), or on AWS. Your own cluster or workstations. No HPSee required.
How you drive it
Point and click in SeeSAR. No scripting required. Python functions that wrap the REST endpoints, with a C-S-D workflow notebook and an administrative notebook. Swagger documentation is available in the browser. Shell commands calling SynthonPrepper, SynthonDocker, and SynthonExtender.
Setup and expertise
HPSee setup on a dedicated machine or server. IT support recommended for maintenance. HPSee setup required, plus working Python knowledge. Binding site and pharmacophore constraints are still set up in SeeSAR. No HPSee setup. Advanced technical expertise required, since you manage orchestration and parallelization.
Flexibility
Guided workflow with visual control and pose inspection at every step. Less restrictive than the GUI, so more steps can be automated. Integrates with your own scripts and libraries such as RDKit. Export and reintroduce data at defined stages, keeping the molecule name and key SD tags, and plug in tools such as PyMOL and RDKit.
Best for
Medicinal and computational chemists who want to stay hands-on and in full visual control. Computational scientists who want automation and flexibility without managing the full infrastructure. Advanced teams that run their own infrastructure and want C-S-D embedded in existing pipelines.
How to access
Download SeeSAR 15 Available upon request.

Request information

 In development. Soon available to early adopters.

Register your interest
Overview Deployment Options [PDF]
Help
Starter Package More Guides

Tutorial videos

FAQ

  • Download SeeSAR 15
    • Begin by downloading the latest version of SeeSAR 15. This software provides the main interface for Chemical Space Docking® (C-S-D), where you’ll manage your compound screenings and interact with the docking tools.
  • Download HPSee 2.3
    • Next, download HPSee 2.3, a companion tool designed for high-performance docking calculations. HPSee handles the heavy lifting for docking operations, allowing you to run large-scale screenings on a dedicated machine or server.
  • Download the CSD Starter Package
    • The C-S-D Starter Pack includes essential resources, including two setup guides and the ROCK-1 Test Space—a sample chemical space for testing C-S-D.
  • Follow the HPSee Deployment Guide
    • Install HPSee 2.3 on your dedicated machine using the detailed steps in the HPSee Deployment Guide. This setup ensures HPSee is ready to handle the docking tasks as you use SeeSAR for screening.
  • Refer to the SeeSAR Beginner Guide
    • Install SeeSAR 15 on your primary workstation and follow the SeeSAR Beginner Guide to get familiar with its interface and workflows. This guide covers the basics of navigating SeeSAR, initiating docking runs, and working with the 3D visualization tools.
  • Watch the Tutorial Video
    • If you need further assistance, the SeeSAR 14 Tutorial Video provides a visual walkthrough of setting up and using C-S-D in SeeSAR, ideal for new users.

Requirements for C-S-D

Category Requirement Details
HPSee Server — Minimum Hardware Requirements
Memory (RAM) 32 GB minimum Approximately 2 GB per CPU core
CPU Cores 32 cores minimum Approximately 5–6 days per C-S-D run
Disk Space 500 GB minimum Allow at least 10 GB per C-S-D project
HPSee Server — Operating-System Support
Linux Supported Docker Engine required
Windows Supported Windows 10 or later, WSL2 and Docker Desktop
macOS Not currently supported HPSee server installations are not currently supported on macOS
SeeSAR Client Requirements
Memory (RAM) 16 GB Required for working with C-S-D results in SeeSAR
Operating Systems Fully supported Linux, macOS and Windows

Get the Chemical Spaces

Download here
Science

"Bigger is Better for Virtual Screening."

A Benchmark Set of Bioactive Molecules for Diversity Analysis of Compound Libraries and Combinatorial Chemical Spaces.
Neumann, A.; Klein, R.
Journal of Chemical Information and Modeling 2025, 65 (17), 9097-9124.
Bigger is better in virtual drug screens.
Gloriam, D.E.
Nature 2019, 566 (7743), 193-194.
Exploration of Ultralarge Compound Collections for Drug Discovery.
Warr, W.A.; Nicklaus, M.C.; Nicolaou, C.A.; Rarey, M.
Journal of Chemical Information and Modeling 2022, 62 (9), 2021-2034.

"Only a Fraction of Brute-Force Resources Is Required."

Computational approaches streamlining drug discovery.
Sadybekov, A.V.; Katritch, V.
Nature 2023, 616 (7958), 673-685.
Chemical space docking enables large-scale structure-based virtual screening to discover ROCK1 kinase inhibitors.
Beroza, P.; Crawford, J.J.; Ganichkin, O.; Gendelev, L.; Harris, S.F.; Klein, R.; Miu, A.; Steinbacher, S.; Klingler, F.; Lemmen, C.
Nature Communications 2022, 13 (1).
Structure-based virtual screening of ultra-large chemical spaces: Advances and pitfalls.
Sindt, F.; Rognan, D.
European Journal of Medicinal Chemistry 2026, 305, 118576.

"Chemical Space Docking® Retrieves Novel Chemotypes."

Magnet for the Needle in Haystack: “Crystal Structure First” Fragment Hits Unlock Active Chemical Matter Using Targeted Exploration of Vast Chemical Spaces.
Müller, J.; Klein, R.; Tarkhanova, O.; Gryniukova, A.; Borysko, P.; Merkl, S.; Ruf, M.; Neumann, A.; Gastreich, M.; Moroz, Y.S.; Klebe, G.; Glinca, S.
Journal of Medicinal Chemistry 2022, 65 (23), 15663-15678.
Integrating 19Focused Screening with Make‐On‐Demand Chemical Spaces for Enhanced Fragment Follow‐Up.
Penner, P.; Henry, C.; Schröder, M.; Vulpetti, A.
ChemMedChem 2026, 21 (11).
Chemical space docking enables large-scale structure-based virtual screening to discover ROCK1 kinase inhibitors.
Beroza, P.; Crawford, J.J.; Ganichkin, O.; Gendelev, L.; Harris, S.F.; Klein, R.; Miu, A.; Steinbacher, S.; Klingler, F.; Lemmen, C.
Nature Communications 2022, 13 (1).

"SAR-by-Catalog Enables Rapid Follow-Up."

SAR by Space: Enriching Hit Sets from the Chemical Space.
Klingler, F.; Gastreich, M.; Grygorenko, O.; Savych, O.; Borysko, P.; Griniukova, A.; Gubina, K.; Lemmen, C.; Moroz, Y.
Molecules 2019, 24 (17), 3096.
The ‘Big Bang’ of the chemical universe.
Cherkasov, A.
Nature Chemical Biology 2023, 19 (6), 667-668.
Magnet for the Needle in Haystack: “Crystal Structure First” Fragment Hits Unlock Active Chemical Matter Using Targeted Exploration of Vast Chemical Spaces.
Müller, J.; Klein, R.; Tarkhanova, O.; Gryniukova, A.; Borysko, P.; Merkl, S.; Ruf, M.; Neumann, A.; Gastreich, M.; Moroz, Y.S.; Klebe, G.; Glinca, S.
Journal of Medicinal Chemistry 2022, 65 (23), 15663-15678.

"Better Scoring Candidates Emerge."

Modeling the expansion of virtual screening libraries.
Lyu, J.; Irwin, J.J.; Shoichet, B.K.
Nature Chemical Biology 2023, 19 (6), 712-718.
Chemical space docking enables large-scale structure-based virtual screening to discover ROCK1 kinase inhibitors.
Beroza, P.; Crawford, J.J.; Ganichkin, O.; Gendelev, L.; Harris, S.F.; Klein, R.; Miu, A.; Steinbacher, S.; Klingler, F.; Lemmen, C.
Nature Communications 2022, 13 (1).
The impact of library size and scale of testing on virtual screening.
Liu, F.; Mailhot, O.; Glenn, I.S.; Vigneron, S.F.; Bassim, V.; Xu, X.; Fonseca-Valencia, K.; Smith, M.S.; Radchenko, D.S.; Fraser, J.S.; Moroz, Y.S.; Irwin, J.J.; Shoichet, B.K.
Nature Chemical Biology 2025, 21 (7), 1039-1045.

Success Stories of Chemical Space Docking®


In collaboration with Genentech, the CSD approach was applied to identify inhibitors of ROCK1 kinase from almost one billion commercially available synthesis-on-demand compounds. From 69 purchased compounds, 27 (39%) had Ki values <10 µM. Two leads were crystallized with the ROCK1 protein, and the structures showed excellent agreement with the docked poses.
Chemical space docking enables large-scale structure-based virtual screening to discover ROCK1 kinase inhibitors.
Beroza, P.; Crawford, J.J.; Ganichkin, O.; Gendelev, L.; Harris, S.F.; Klein, R.; Miu, A.; Steinbacher, S.; Klingler, F.; Lemmen, C.
Nature Communications 2022, 13 (1).

Starting from four small molecule fragment complexes of Protein Kinase A (PKA), CSD was performed in collaboration with Crystals First to screen for novel inhibitor chemotypes. Out of the 93 synthesized molecules, 40 (43%) were active. The best follow up of the fragments displayed a 13,500-fold gain in affinity and six X-ray crystal structures were obtained. The whole process took only nine weeks.
Magnet for the Needle in Haystack: “Crystal Structure First” Fragment Hits Unlock Active Chemical Matter Using Targeted Exploration of Vast Chemical Spaces.
Müller, J.; Klein, R.; Tarkhanova, O.; Gryniukova, A.; Borysko, P.; Merkl, S.; Ruf, M.; Neumann, A.; Gastreich, M.; Moroz, Y.S.; Klebe, G.; Glinca, S.
Journal of Medicinal Chemistry 2022, 65 (23), 15663-15678.
Workflow Insights

Getting Started: Anchoring of Synthons

The workflow starts with the docking of the building blocks that are used in the creation of the selected Chemical Space.
In this step, you have the opportunity to apply pharmacophore constraints at your defined binding site. This will guide the placement of synthons (the initial starting fragments for compounds) and identify those capable of forming desired interactions with the target.

Once the synthons have been docked, you can examine the produced poses with the visual support provided by SeeSAR. Each synthon is equipped with a marker indicating its extension direction, referred to as a 'linker atom', thereby simplifying the evaluation process.

The chosen candidates then move forward to the next phase of the workflow: the extension stage.

Extension of Synthons: Evolving into Drug Candidates

After the anchoring phase, selected synthons expand into drug-like compounds during the extension stage. Here, the initial fragments are combined with other building blocks following chemical reaction rules of the Chemical Space. Only compounds that can be synthesized are created and assessed for their interactions at the binding site.
The setup within SeeSAR swiftly processes the docking of the extended compounds with precision to ensure they mirror the binding mode of the synthon starting point. This approach is several times faster than conventional docking methods and guarantees that the evolved compounds match the orientation of your starting fragment.

Again, you as a user can guide the process with pharmacophore constraints to introduce additional interaction patterns into the results.

Once the calculations have finished, you are presented with results of two kinds: Compounds with a linker and those without a linker. Compounds without a linker are final molecules that can be ordered or synthesized. Compounds still containing a linker require an additional extension run that will lead to final molecules.

Available Chemical Spaces

Download page Vendor Size Order compounds at
Commercial Chemical Spaces [Info]
VAST™ XtalPi 4.7 × 10⁹ sales@aifchem.com
AuriVerse Aurigene 4.9 × 10⁹ contactapsl@aurigeneservices.com
GalaXi WuXi LabNetwork 2.6 × 10¹⁰ contact@labnetwork.com
CHEMriya OTAVAchemicals 5.5 × 10¹⁰ info@otava.ca
REAL Space Enamine Ltd. 9.5 × 10¹⁰ libraries@enamine.net
AMBrosia Ambinter (Greenpharma) 1.3 × 10¹¹ ambrosia@greenpharma.com
Freedom Space Chemspace 3.0 × 10¹¹ sales@chem-space.com
xREAL Space Enamine 4.4 × 10¹² libraries@enamine.net
eXplore eMolecules 8.3 × 10¹² explore@emolecules.com
Synple Space Synple Chem 8.3 × 10¹² order@synplechem.com
Virtual Chemical Spaces
KnowledgeSpace BioSolveIT (virtual) 2.6 × 10¹⁴
SAVI Space BioSolveIT (virtual), Enamine* 7.5 × 109 libraries@enamine.net*

Ready to explore Chemical Space Docking®?

Spotlight SeeSAR 14 Read more about C-S-D (PDF)