Computational Screeing and Docking Tool (SLIDE)

Introduction SLIDE (Screening for Ligands by Induced Fit Docking Efficiently) represents a general approach to organic and peptidyl database screening. It can handle large binding-site templates and uses multi-stage indexing to identify feasible subsets of template points for ligand docking. An optimization approach based on mean-field theory is applied to model induced-fit complementarity, balancing flexibility between the ligand and the protein side chains. SLIDE can screen 100,000 compounds within a few days and returns a ranked list of sterically feasible ligand candidates, ranked by complementarity to the protein's binding site.  Description of Technology The invention is a computational screening and docking took designed to find ligands with good steric and chemical complementarity to the known three-dimensional structure of a protein's binding site. The binding site is represented by a template with hydrophobic and hydrogen bonding points. Multistep indexing quickly tests all possible matchings of hydrophobic and hydrogen bonding interaction centers on each ligand candidate with the protein template. Key BenefitsBalanced protein-ligand flexibilityPharmacophore-based or full binding site templateScreens, docks, and scores 100,000 molecules in ~2 days on desktop hardwareRuns on Unix workstations using C or PerlIncludes source codeCan screen any small-molecule database formatted as mol2 files. For ligands that are highly flexible or have 3D structures constructed from 2D, conformational sampling is recommended as input to SLIDE. Patent Status Patent pending Inventors Leslie Kuhn, Volker Schnecke, Paul Sanschagrin, Maria Zavodszky, Matthew Tonero Tech ID TEC1995-0097

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