title: Application of Enhanced Sampling Monte Carlo Methods for High-Resolution Protein-Protein Docking in Rosetta.
abstract: The high-resolution refinement of docked protein-protein complexes can provide valuable structural and mechanistic insight into protein complex formation complementing experiment. Monte Carlo (MC) based approaches are frequently applied to sample putative interaction geometries of proteins including also possible conformational changes of the binding partners. In order to explore efficiency improvements of the MC sampling, several enhanced sampling techniques, including temperature or Hamiltonian replica exchange and well-tempered ensemble approaches, have been combined with the MC method and were evaluated on 20 protein complexes using unbound partner structures. The well-tempered ensemble method combined with a 2-dimensional temperature and Hamiltonian replica exchange scheme (WTE-H-REMC) was identified as the most efficient search strategy. Comparison with prolonged MC searches indicates that the WTE-H-REMC approach requires approximately 5 times fewer MC steps to identify near native docking geometries compared to conventional MC searches.
authors.affiliation: Physik-Department T38, Technische Universität München, James-Franck-Str. 1, 84748 Garching, Germany.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Physik-Department T38, Technische Universität München, James-Franck-Str. 1, 84748 Garching, Germany.
authors.forename: Christina E M
authors.initials: CE
authors.lastname: Schindler
authors.affiliation: Biomolecular NMR and Munich Center for Integrated Protein Science, Department Chemie, Technische Universität München, Lichtenbergstr. 4, 85748 Garching, Germany.
authors.forename: Oliver F
authors.initials: OF
authors.lastname: Lange
authors.affiliation: Physik-Department T38, Technische Universität München, James-Franck-Str. 1, 84748 Garching, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zacharias
mesh_terms: D062105:Molecular Docking Simulation; D009010:Monte Carlo Method; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D012984:Software; D013816:Thermodynamics; D057188:Workflow
chemical_list: D011506:Proteins