Available Technologies

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

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.

Benefits

* Balanced protein-ligand flexibility

* Pharmacophore-based or full binding site template

* Screens, docks, and scores 100,000 molecules in ~2 days on desktop hardware

* Runs on Unix workstations using C or Perl

* Includes source code

* Can 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.