Blind docking has been widely used for fast mapping of binding sites on the entire surface of drug targets. Reliability of blind docking is limited by approximations of hydration models, simplified handling of molecular flexibility, and imperfect search algorithms. Wrap and Shake (WnS), a systematic, atomic resolution method was developed to overcome such limitations of blind docking. The poster presentation features how WnS systematically wraps the entire target into a monolayer of ligand molecules and extracts functional binding sites by rapid molecular dynamics shakers. WnS was validated on biologically important systems such as mitogen-activated protein, tyrosine-protein kinases, key players of cellular signaling, and farnesyl pyrophosphate synthase, a target of antitumor agents.
Audience take away:
WnS is a systematic method which predicts stable positions of ligands on the target surface. WnS combines the advantages of a fast docking, with the precision of explicit solvent molecular dynamics. WnS is freely available, and automatized. WnS works is synergy with popular open source program packages AutoDock and Gromacs. We envision that WnS can become the tool of choice for systematic exploration of multiple binding sites and modes of ligands in drug design and structural biology.