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 the desired biological activity (lead hopping or scaffold hopping). Ligand based virtual screening for structures with similar shape and/or pharmacophore features is an 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 a fast 3D ligand-based virtual screening tool 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 consider molecules’ shape, H-bonding, and electrostatic properties. Shape similarity, as computed by Surflex-Sim, is an effective way to predict both on- and off-target pharmacological effects.
  • UNITY-3D is an industry standard with thousands of literature publications demonstrating successful lead discovery based on its conformationally flexible pharmacophore based searching. UNITY’s rich set of pharmacophore features enable 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 the drug target’s structure isn’t known. The pharmacophore models are useful for virtual screening and for inspiring and testing new ideas to see how they match to a set of lead drug candidates.

Learn more about the SYBYL-X Suite:

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