Performance of MDockPP in CAPRI rounds 28-29 and 31-35 including the prediction of water-mediated interactions.
Protein-protein interactions are either through direct contacts between two binding partners or mediated by structural waters. Both direct contacts and water-mediated interactions are crucial to the formation of a protein-protein complex. During the recent CAPRI rounds, a novel parallel searching strategy for predicting water-mediated interactions is introduced into our protein-protein docking method, MDockPP. Briefly, a FFT-based docking algorithm is employed in generating putative binding modes, and an iteratively derived statistical potential-based scoring function, ITScorePP, in conjunction with biological information is used to assess and rank the binding modes. Up to 10 binding modes are selected as the initial protein-protein complex structures for MD simulations in explicit solvent. Water molecules near the interface are clustered based on the snapshots extracted from independent equilibrated trajectories. Then, protein-ligand docking is employed for a parallel search for water molecules near the protein-protein interface. The water molecules generated by ligand docking and the clustered water molecules generated by MD simulations are merged, referred to as the predicted structural water molecules. Here, we report the performance of this protocol for CAPRI rounds 28-29 and 31-35 containing 20 valid docking targets and 11 scoring targets. In the docking experiments, we predicted correct binding modes for nine targets, including one high-accuracy, two medium-accuracy, and six acceptable predictions. Regarding the two targets for the prediction of water-mediated interactions, we achieved models ranked as "excellent" in accordance with the CAPRI evaluation criteria; one of these two targets is considered as a difficult target for structural water prediction. Proteins 2017; 85:424-434. © 2016 Wiley Periodicals, Inc.
Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, 65211, USA.
Xianjin
X
Xu
Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, 65211, USA.
Liming
L
Qiu
Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, 65211, USA.|Department of Physics and Astronomy, University of Missouri, Columbia, Missouri, 65211, USA.
Chengfei
C
Yan
Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, 65211, USA.|Department of Physics and Astronomy, University of Missouri, Columbia, Missouri, 65211, USA.
Zhiwei
Z
Ma
Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, 65211, USA.|Informatics Institute, University of Missouri, Columbia, Missouri, 65211, USA.
Sam Z
SZ
Grinter
Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, 65211, USA.|Department of Physics and Astronomy, University of Missouri, Columbia, Missouri, 65211, USA.|Department of Biochemistry, University of Missouri, Columbia, Missouri, 65211, USA.|Informatics Institute, University of Missouri, Columbia, Missouri, 65211, USA.
Xiaoqin
X
Zou
D000465:Algorithms; D019985:Benchmarking; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D062105:Molecular Docking Simulation / Q000379:methods*; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D055503:Protein Multimerization; D011506:Proteins / Q000737:chemistry*; D012107:Research Design; D012984:Software; D040681:Structural Homology, Protein; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
D011506:Proteins; D014867:Water
molecular docking; molecular dynamics simulations. scoring function; protein-protein interactions; water-mediated interactions