A Fragment-Based Scoring Function to Re-rank ATP Docking Results

Abstract: ATP is involved in numerous biochemical reactions in living cells interacting withdifferent proteins. Molecular docking simulations provide considerable insight into theproblem of molecular recognition of this substrate. To improve the selection of correctATP poses among those generated by docking algorithms we propose a post-docking rerankingcriterion. The method is based on detailed analysis of the intermolecularinteractions in 50 high-resolution 3D-structures of ATP-protein complexes. A distinctivenew feature of the proposed method is that the ligand molecule is divided into fragmentsthat differ in their physical properties. The placement of each of them into the bindingsite is judged separately by different criteria, thus avoiding undesirable averaging of thescoring function terms by highlighting those relevant for particular fragments. Thescoring performance of the new criteria was tested with the docking solutions for ATPproteincomplexes and a significant improvement in the selection of correct dockingposes was observed, as compared to the standard scoring function.