Ligand Based Virtual Screening
Shape Based Similarity and Alignment, Pharmacophore Searching
For Lead Identification, researchers need to be able to identify novel structures, scaffolds, or R-groups that have an improved chance of showing the desired biological activity (lead hopping or scaffold hopping). Ligand based virtual screening for structures with similar shape and/or pharmacophore features has been shown to be a highly successful and efficient method for identifying novel active compounds for Lead Identification, as well as for lead expansion, lead hopping and scaffold hopping.
The SYBYL-X Suite includes a comprehensive set of tools for shape and pharmacophore based analysis and virtual screening:
- Topomer Search is an exceptionally fast 3D ligand-based virtual screening tool that has been demonstrated to be effective for both lead hopping and scaffold hopping. Topomer Search can search millions of structures overnight on a single processor, allowing you to screen very large collections of compounds and avoid the risk of missing important leads because of subsetting. Screen for whole molecules, side chains, or scaffolds using conformationally independent topomer similarity.
- Surflex-Sim performs rigorous, flexible 3D shape based virtual screening. In addition, the molecular alignments and hypotheses of bioactive ligand conformations generated by Surflex-Sim stimulate 3-D ligand-based design. Surflex-Sim's comprehensive shape comparison algorithms include the consideration of the molecules’ shape, H-bonding, and electrostatic properties. Shape similarity, as computed by Surflex-Sim has been shown to be highly effective as means of rationalizing and predicting both on- and off-target pharmacological effects.
- UNITY-3D is an industry standard with literally thousands of literature publications demonstrating successful lead discovery based on UNITY's conformationally flexible pharmacophore based searching. UNITY's rich set of pharmacophore features enable highly specific queries to be constructed from a lead structure, a pharmacophore model, or a receptor active site.
- Galahad, GASP, and DiscoTech are pharmacophore hypothesis generation tools that deduce the spatial requirements for drug binding when a structure of the drug’s target isn’t known. The pharmacophore models that are generated are useful for virtual screening and for inspiring and testing new ideas to see how they match to a set of lead drug candidates.
- Screen millions of structures overnight
- Screen large collections withoutthe need for subsetting - avoid the risk of missing leads
- Use all known leads as queries because multiple query searchesare fast and efficient
- Virtually independent of query and database conformations
- No feature mapping input or guidance is required
- Requires no template definition
- No protein preparation is needed
- Effective for Virtual Screening as demonstrated by numerous publications
- Effective for Lead Hopping andScaffold Hopping
- Use Topomer Search in concert with Topomer CoMFA® to identify the substituents and R-groups that are predicted to optimize the activity of your compounds
EFFECTIVE AND RIGOROUS
- Highly effective for virtual screening as demonstrated by numerous publications
- Demonstrated to identify non-trivial scaffold and lead hops that cannot be identified on the basis of 2D similarities
- Generates compelling 3D molecular alignments and hypotheses of bioactive ligand conformations
- Surflex-Sim's shape comparison algorithms include the consideration of the molecules’ shape, H-bonding, and electrostatic properties
ON-TARGET and OFF TARGET SCREENING
- Shown to be highly effective as means of rationalizing and predicting both on- and off-target pharmacological effects
FOCUSED, HIGHLY SPECIFIC 3D SCREENING
- Screen for ligands that fit a receptor site and interact with key receptor pharmacophores
- Highly specific 3D queries can be constructed from an extensive set of features and constraints
- Partial matching of query features provide flexibility to specify how many interactions are needed
- Queries contain realistic hydrogen bond donor/acceptor site representations
- Create pharmacophore and alignment models from diverse sets of flexible, active compounds
- Generating models that are sterically, pharmacophorically, and energetically optimal
- Provides a variety of high quality models according to different criteria
- Allows the user can to select which criteria are most important