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Performance of MDockPP in CAPRI rounds 28‐29 and 31‐35 including the prediction of water‐mediated interactions
Author(s) -
Xu Xianjin,
Qiu Liming,
Yan Chengfei,
Ma Zhiwei,
Grinter Sam Z.,
Zou Xiaoqin
Publication year - 2017
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.25203
Subject(s) - docking (animal) , macromolecular docking , computer science , surface protein , searching the conformational space for docking , molecule , protein–protein interaction , biological system , binding pocket , computational biology , molecular dynamics , protein structure , chemistry , computational chemistry , binding site , biology , biochemistry , medicine , nursing , organic chemistry , virology
ABSTRACT 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.

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