title: Ranking protein-protein docking results using steered molecular dynamics and potential of mean force calculations.
abstract: Crystallization of protein-protein complexes can often be problematic and therefore computational structural models are often relied on. Such models are often generated using protein-protein docking algorithms, where one of the main challenges is selecting which of several thousand potential predictions represents the most near-native complex. We have developed a novel technique that involves the use of steered molecular dynamics (sMD) and umbrella sampling to identify near-native complexes among protein-protein docking predictions. Using this technique, we have found a strong correlation between our predictions and the interface RMSD (iRMSD) in ten diverse test systems. On two of the systems, we investigated if the prediction results could be further improved using potential of mean force calculations. We demonstrated that a near-native (<2.0 Å iRMSD) structure could be identified in the top-1 ranked position for both systems. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 Stadium Mall Drivem, West Lafayette, Indiana, 47907.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Kingsley
authors.affiliation: Department of Computer Science, Purdue University, 305 North University Street, West Lafayette, Indiana, 47907.
authors.forename: Juan
authors.initials: J
authors.lastname: Esquivel-Rodríguez
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 Stadium Mall Drivem, West Lafayette, Indiana, 47907.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Computer Science, Purdue University, 305 North University Street, West Lafayette, Indiana, 47907.|Department of Biological Sciences, Purdue University, 249 South Martin Jischke Drive, West Lafayette, Indiana, 47907.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kihara
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 Stadium Mall Drivem, West Lafayette, Indiana, 47907.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Lill
mesh_terms: D008956:Models, Chemical; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D011506:Proteins
keywords: ZDOCK; potential of mean force; protein-protein interaction; steered molecular dynamics; umbrella sampling