Virtual Screening Software

Virtual Screening: Your Drug Discovery Accelerator

Virtual screening is a computational approach that predicts potential binders from large molecular datasets—often comprising millions, billions, or even trillions of compounds.
It mines for the most promising candidates for experimental validation and thus minimizes experimental costs and maximizes efficiency in the early phases of drug discovery.

Given a set of compounds, binding poses for each molecule at a target's binding site are generated and assessed for their formed interactions, leading to a numerical score. By ranking each pose based on it's score, compound with increased likelihood to form high-quality interactions with the target enrich in the top ranks. This is applied in early stages of drug discovery to focus on the compounds most likely to display biological activity by binding to a the structure of interest. After visual assessment of the virtual screening results, a selection of chemically diverse compounds is made to be tested, reducing the required resources to only a fraction of evaluating every single compound from the molecule set.

Smarter Screening, Better Results

The success of virtual screening depends on the quality and diversity of the molecular libraries utilized. These libraries can be built from:

Ultra-Large Chemical Spaces: The largest compound hunting grounds going beyond the limits of enumerated molecule libraries, created with building blocks and chemical reactions on how to combine them.
Commercially-Offered Compound Libraries: Extensive collections of compounds available for purchase.
Target-Focused Libraries: Curated sets of molecules designed with a specific biological target in mind that enhance the likelihood of identifying active compounds.
Natural Compounds: Molecules derived from natural sources, providing unique structural features not commonly found in synthetic libraries.
Collaborations: Partnerships with research institutions that contribute specialized compound collections, facilitating innovation through shared knowledge.

Accelerate Your Virtual Screening

Our solutions make virtual screening smarter, faster, and more intuitive. Our tools integrate seamlessly into existing workflows, helping you identify quality hits with ease.

SeeSAR: The ultimate drug design dashboard, putting structure-based design at your fingertips. SeeSAR lets you visualize binding interactions, assess docking results, and refine compounds in real time—all in an intuitive interface.
HPSee: A powerhouse for high-throughput docking, built for speed and scale. HPSee facilitates screening of massive molecular libraries efficiently, ensuring top candidates rise to the surface without compromising on computational resources.

Next-Generation Virtual Screening: Chemical Space Docking™

Chemical Space Docking™ (C-S-D) is a novel structure-based virtual screening method that screens ultra-vast Chemical Spaces containing billions or more for the most promising drug candidates.
Users can conveniently start their C-S-D workflow in SeeSAR's visual interface. HPSee then takes over the calculations and the preparation of the results.
The initial anchoring of synthons can be enhanced by using co-crystallized ligands or predicted binding poses from docking studies as templates for pose generation. This approach accelerates calculations while producing poses that are structurally aligned with the template molecule.

Learn more about C-S-D.
Read more about C-S-D here (PDF).
Learn more about C-S-D in SeeSAR 14 Atlas.

Command-Line Tools for Docking and Scoring

Pose Generation (FlexX) Provides efficient exploration of conformational space, generating credible ligand orientations in the binding site.
Affinity Prediction (HYDE):Adds a deeper layer of evaluation by considering hydration, intramolecular strain, and the precise balance of energetics.

Combining FlexX and HYDE often gives a more robust prediction of ligand binding. FlexX’s pose generation plus HYDE’s scoring can streamline hit discovery, lead optimization, and beyond.

Additional Insights from HYDE

Hydrogen Network Optimization: HYDE excels at revealing opportunities to optimize the hydrogen-bond network. Even subtle changes to the ligand or target—like adding a small polar group—can profoundly improve binding.
Chalcogen Bonds: HYDE accounts for emerging interaction types, including chalcogen bonds (e.g., NH–O, NH–S), which are increasingly recognized for their importance in medicinal chemistry.
Visual Assessment & Spheres: By visualizing the interaction spheres, you quickly spot regions where compound modifications could enhance affinity or improve physicochemical properties. A traffic-light scheme (green–amber–red) further flags poses that are particularly promising or warrant caution.

Ligand-Based Virtual Screening: Finding Hits in 2D

BioSolveIT software for analog mining:

infiniSee: Chemical Space navigation platform with a graphical user interface.
With its Scaffold Hopper, Analog Hunter and Motif Matcher Modes, infiniSee searches for related compounds to your query compound inside ultra-large Chemical Spaces. Respectively, it screens for similar compounds based on molecular fingerprints and the maximum common substructure which both can be considered as valid methods to retrieve analogs.
infiniSee xREAL: Exclusive platform to screen Enamine's largest compound catalog featuring trillions of compounds.

Command-line tools for Chemical Space exploration:

FTrees: Mines for similar compounds based on fuzzy pharmacophore features. Algorithm behind the Scaffold Hopper Mode.
SpaceLight: Retrieves close analogs based on molecular fingerprints. Algorithm behind the Analog Hunter Mode.
SpaceMACS: Performs maximum common substructure searches, as well as exact substructure mining. Algorithm behind the Motif Matcher Mode.

Additional Considerations

When picking analogs for synthesis or purchasing, keep the chemical diversity in mind. It is better to explore a broad range of functionalities to cover a larger area of the Chemical Space. Focusing on particular parts of the molecule is always possible if required.
Keep an eye on the physicochemical and ADME properties during planing of the next steps.
Use pharmacophore constraints during ideation to collect proposals for potential bioisosters. "Ring system" constraints can help you to rigidify your molecule.
In order to include selectivity aspects into your design, align the binding sites of your targets with other members of its family and its off-targets. Also dock your compound into the respective aligned binding sites for insights.
Endogenous ligands typically are accompanied with a series of reported analogs that help you establish SARs and identify important interactions. Check for literature to enhance your data set.

Excited for more drug discovery solutions?

Keep on exploring!