Protein-Protein Docking with F2Dock 2.0 and GB-Rerank

Rezaul Chowdhury is with UT Austin; Muhibur Rasheed is with UT Austin; Maysam Moussalem is with UT Austin; Donald Keidel is with The Scripps Research Institute; Arthur Olson is with The Scripps Research Institute; Michel Sanner is with The Scripps Research Institute; Chandrajit Bajaj is with The Scripps Research Institute.Motivation -- Computational simulation of protein-protein docking can expedite the process of molecular modeling and drug discovery. This paper reports on our new F2 Dock protocol which improves the state of the art in initial stage rigid body exhaustive docking search, scoring and ranking by introducing improvements in the shape-complementarity and electrostatics affinity functions, a new knowledge-based interface propensity term with FFT formulation, a set of novel knowledge-based filters and finally a solvation energy (GBSA) based reranking technique. Our algorithms are based on highly efficient data structures including the dynamic packing grids and octrees which significantly speed up the computations and also provide guaranteed bounds on approximation error. Results -- The improved affinity functions show superior performance compared to their traditional counterparts in finding correct docking poses at higher ranks. We found that the new filters and the GBSA based reranking individually and in combination significantly improve the accuracy of docking predictions with only minor increase in computation time. We compared F2 Dock 2.0 with ZDock 3.0.2 and found improvements over it, specifically among 176 complexes in ZLab Benchmark 4.0, F2 Dock 2.0 finds a near-native solution as the top prediction for 22 complexes; where ZDock 3.0.2 does so for 13 complexes. F2 Dock 2.0 finds a near-native solution within the top 1000 predictions for 106 complexes as opposed to 104 complexes for ZDock 3.0.2. However, there are 17 and 15 complexes where F2 Dock 2.0 finds a solution but ZDock 3.0.2 does not and vice versa; which indicates that the two docking protocols can also complement each other. Availability -- The docking protocol has been implemented as a server with a graphical client (TexMol) which allows the user to manage multiple docking jobs, and visualize the docked poses and interfaces. Both the server and client are available for download. Server: http://www.cs.utexas.edu/~bajaj/cvc/soft​ware/f2dock.shtml. Client: http://www.cs.utexas.edu/~bajaj/cvc/soft​ware/f2dockclient.shtml.The research of C.B., R.C., M.M., and M.R. of University of Texas, was supported in part by National Science Foundation (NSF) grant CNS-0540033, and grants from the National Institutes of Health (NIH) R01-GM074258, R01-GM073087, R01-EB004873. The research of M.M. was additionally supported by an NSF Graduate Research Fellowship. The research of M.S. and A.O. of TSRI was supported in part by a subcontract on NIH grant R01-GM073087. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Computer Science

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