Monte Carlo replica-exchange based ensemble docking of protein conformations.
A replica-exchange Monte Carlo (REMC) ensemble docking approach has been developed that allows efficient exploration of protein-protein docking geometries. In addition to Monte Carlo steps in translation and orientation of binding partners, possible conformational changes upon binding are included based on Monte Carlo selection of protein conformations stored as ordered pregenerated conformational ensembles. The conformational ensembles of each binding partner protein were generated by three different approaches starting from the unbound partner protein structure with a range spanning a root mean square deviation of 1-2.5 Å with respect to the unbound structure. Because MC sampling is performed to select appropriate partner conformations on the fly the approach is not limited by the number of conformations in the ensemble compared to ensemble docking of each conformer pair in ensemble cross docking. Although only a fraction of generated conformers was in closer agreement with the bound structure the REMC ensemble docking approach achieved improved docking results compared to REMC docking with only the unbound partner structures or using docking energy minimization methods. The approach has significant potential for further improvement in combination with more realistic structural ensembles and better docking scoring functions. Proteins 2017; 85:924-937. © 2016 Wiley Periodicals, Inc.
Physik-Department T38, Technische Universität München, Garching, 85748, Germany.|Department Chemie, Technische Universität München, Biomolecular NMR and Munich Center for Integrated Protein Science, Garching, 85747, Germany.|College of Life and Health Sciences, Northeast University, Shenyang, P.R. China.
Zhe
Z
Zhang
Physik-Department T38, Technische Universität München, Garching, 85748, Germany.
Uwe
U
Ehmann
Physik-Department T38, Technische Universität München, Garching, 85748, Germany.
Martin
0000-0001-5163-2663
M
Zacharias
D001665:Binding Sites; D062105:Molecular Docking Simulation; D009010:Monte Carlo Method; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
D011506:Proteins
advanced sampling simulations; protein complex formation; protein-protein interaction; receptor-ligand docking; replica exchange approaches