title: pyDock: electrostatics and desolvation for effective scoring of rigid-body protein-protein docking.
abstract: The accurate scoring of rigid-body docking orientations represents one of the major difficulties in protein-protein docking prediction. Other challenges are the development of faster and more efficient sampling methods and the introduction of receptor and ligand flexibility during simulations. Overall, good discrimination of near-native docking poses from the very early stages of rigid-body protein docking is essential step before applying more costly interface refinement to the correct docking solutions. Here we explore a simple approach to scoring of rigid-body docking poses, which has been implemented in a program called pyDock. The scheme is based on Coulombic electrostatics with distance dependent dielectric constant, and implicit desolvation energy with atomic solvation parameters previously adjusted for rigid-body protein-protein docking. This scoring function is not highly dependent on specific geometry of the docking poses and therefore can be used in rigid-body docking sets generated by a variety of methods. We have tested the procedure in a large benchmark set of 80 unbound docking cases. The method is able to detect a near-native solution from 12,000 docking poses and place it within the 100 lowest-energy docking solutions in 56% of the cases, in a completely unrestricted manner and without any other additional information. More specifically, a near-native solution will lie within the top 20 solutions in 37% of the cases. The simplicity of the approach allows for a better understanding of the physical principles behind protein-protein association, and provides a fast tool for the evaluation of large sets of rigid-body docking poses in search of the near-native orientation.
authors: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
authors: Tammy Man-Kuang
authors: TM
authors: Cheng
authors: Tom L
authors: TL
authors: Blundell
authors: Juan
authors: J
authors: Fernandez-Recio
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D008968:Molecular Conformation; D011485:Protein Binding; D011487:Protein Conformation; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism; D012996:Solutions; D055672:Static Electricity
chemical_list: D002352:Carrier Proteins; D008024:Ligands; D012996:Solutions; D020794:Receptor Protein-Tyrosine Kinases