pyDock: Electrostatics and desolvation for effective scoring of rigid-body protein-protein docking

被引:253
作者
Cheng, Tammy Man-Kuang
Blundell, Tom L.
Fernandez-Recio, Juan
机构
[1] Barcelona Supercomp Ctr, Dept Life Sci, E-08034 Barcelona, Spain
[2] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England
[3] Biomed Res Inst, Struct & Computat Biol Dept, E-08028 Barcelona, Spain
关键词
protein-protein association; rigid-body docking; CAPRI; ASA-based desolvation; atomic solvation parameter; binding energy;
D O I
10.1002/prot.21419
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The accurate scoring of rigidbody 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.
引用
收藏
页码:503 / 515
页数:13
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