Toolkit for 2D and 3D molecular screening
The Screen Suite is a ligand-based high throughput virtual screening package that provides powerful tools for chemical (2D) and shape (3D) similarity searches of large molecular libraries. The suite provides several different sets of fingerprints, such as the ChemAxon chemical fingerprint, pharmacophore fingerprint, ECFP/FCFP, dissimilarity metrics and their optimization to tune your processes for optimal search results. Commercially the suite is available as 2D Descriptor package, Screen2D (including our chemical fingerprint) and Screen3D. It is also available as a command line tool, from Java and .NET API and workflow tools like KNIME or Pipeline Pilot. Screen Suite is a progenitor of the novel MadFast similarity search engine, where descriptor generation and similarity search using multiple metrics are also available.
Flexible descriptor accessibility in Screen Suite
The Screen2D Descriptor package contains fingerprint generators for chemical structures, pharmacophores, extended connectivity (ECFP) and functional class (FCFP) descriptors. It can be used to generate and tune fingerprints for use in any screening process. Descriptor generation is supported through ChemAxon’s Chemical Terms scripting language, to create complex fingerprints which consider single or combined molecular attributes that can be based on topological or physicochemical properties like partition coefficients, hydrogen bonding donor-acceptor accessibility or acidic properties.
ChemAxon's screening technology heavily relies on the available chemical fingerprints and molecular descriptors:
- BCUT descriptors - used in diversity analyses and QSAR; based on the connectivity table of molecules with physchem properties like atomic charge, HBDA and polarizability
- Chemical fingerprint - used for structural searches in databases, similarity search or diversity analysis of compound libraries; it is a path-based bit-string descriptor describing molecular structures
- Pharmacophore fingerprints - atom-based fingerprints characterizing binding related structural or physchem properties that are thought to be responsible for pharmacophore activity
- Circular fingerprints - in contrast to path-based fingerprints ECFP/FCFP are not substructure preserving descriptions, but are highly relevant for full structure and similarity searches.
Screen 2D is a robust platform to perform chemical similarity searches on large molecular databases. It offers a fast process with up to 100,000 compounds per second being screened on a single desktop PC. Modularity of the tool allows to use own descriptor sets. Screen 2D comes with a set of metrics to measure dissimilarity between compounds:
Screen 2D supports metrics optimization by selecting appropriate training sets. The optimization step increases enrichment significantly, giving smaller, more focused hit sets. It is available through API and command line, via Pipeline Pilot and KNIME connectors, and some features are implemented within Instant JChem and JChem for Office desktop applications.
Screen Suite includes 3D shape similarity based searching in addition to topology based screening. It introduces a novel flexible alignment technique, which provides reasonable alternative hit results as compared to previous 3D screen engines. The key feature of Screen 3D is definitely its high speed, however, it also compares very well in providing better enrichment in the first 1% of the hits than most alternative software. Scalability of the tool makes it suitable to search in very large molecular databases.
Screen 3D can be used to carry out different shape similarity searches. Beyond fully flexible matching it can align flexible database compounds to rigid query molecules (rigid-flexible). Alternatively it is capable of aligning rigid database compounds to rigid query molecules (rigid-rigid) using on-the-fly generated conformation ensembles. Benefits of Screen3D can also be exploited as a plugin in Marvin Live idea assessment and management platform.