A new method for ligand docking to flexible receptors by dual alanine scanning and refinement (SCARE).

ABSTRACT: Protein binding sites undergo ligand specific conformational changes upon ligand binding. However, most docking protocols rely on a fixed conformation of the receptor, or on the prior knowledge of multiple conformations representing the variation of the pocket, or on a known bounding box for the ligand. Here we described a general induced fit docking protocol that requires only one initial pocket conformation and identifies most of the correct ligand positions as the lowest score. We expanded a previously used diverse "cross-docking" benchmark to thirty ligand-protein pairs extracted from different crystal structures. The algorithm systematically scans pairs of neighbouring side chains, replaces them by alanines, and docks the ligand to each 'gapped' version of the pocket. All docked posit

SUBMITTER: Bottegoni G 

PROVIDER: S-EPMC2641994 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature