title: High-throughput all-atom molecular dynamics simulations using distributed computing.
abstract: Although molecular dynamics simulation methods are useful in the modeling of macromolecular systems, they remain computationally expensive, with production work requiring costly high-performance computing (HPC) resources. We review recent innovations in accelerating molecular dynamics on graphics processing units (GPUs), and we describe GPUGRID, a volunteer computing project that uses the GPU resources of nondedicated desktop and workstation computers. In particular, we demonstrate the capability of simulating thousands of all-atom molecular trajectories generated at an average of 20 ns/day each (for systems of approximately 30 000-80 000 atoms). In conjunction with a potential of mean force (PMF) protocol for computing binding free energies, we demonstrate the use of GPUGRID in the computation of accurate binding affinities of the Src SH2 domain/pYEEI ligand complex by reconstructing the PMF over 373 umbrella sampling windows of 55 ns each (20.5 mus of total data). We obtain a standard free energy of binding of -8.7 +/- 0.4 kcal/mol within 0.7 kcal/mol from experimental results. This infrastructure will provide the basis for a robust system for high-throughput accurate binding affinity prediction.
authors.affiliation: Computational Biochemistry and Biophysics Lab (GRIB-IMIM), Universitat Pompeu Fabra, Barcelona Biomedical Research Park, C/ Doctor Aiguader 88, Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Buch
authors.forename: M J
authors.initials: MJ
authors.lastname: Harvey
authors.forename: T
authors.initials: T
authors.lastname: Giorgino
authors.forename: D P
authors.initials: DP
authors.lastname: Anderson
authors.forename: G
authors.initials: G
authors.lastname: De Fabritiis
mesh_terms: D006801:Humans; D056004:Molecular Dynamics Simulation / Q000191:economics / Q000639:trends; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D013816:Thermodynamics; D018909:src Homology Domains
chemical_list: D009842:Oligopeptides; C487410:phosphotyrosyl-glutamyl-glutamyl-isoleucine