ASEDock -- Fast Docking between Ligands and A Receptor Based on Alpha Spheres and Excluded Volumes

Abstract

Development and validation study of a novel docking program, ASEDock is presented. ASEDock is a fast docking program based on a concave shape alignment method. We have defined ASE Model, a simple but accurate representation of concave shape and ASEScore, which evaluates shape similarity between ASEModel and ligand structure. Initial poses of the ligand were refined based on ASEScore in terms of the maximum overlap to alpha spheres and minimum overlap to receptor atoms, followed by full atomistic energy minimization. Simple function form of ASEScore makes it possible to search all reasonable poses efficiently. Because ASE Model accurately represents concave shape, actual ligand structures of binding mode were found in initial poses with best ASEScore. Since posing algorithm of ASEDock is free from any bias except shape, it is a very robust docking method. Validation study has demonstrated that ASEDock can reproduce experimentally determined docking mode of the complex that has no strong interaction, such as hydrogen bond, between ligand and receptor.