title: Large-scale asynchronous and distributed multidimensional replica exchange molecular simulations and efficiency analysis.
abstract: We describe methods to perform replica exchange molecular dynamics (REMD) simulations asynchronously (ASyncRE). The methods are designed to facilitate large scale REMD simulations on grid computing networks consisting of heterogeneous and distributed computing environments as well as on homogeneous high-performance clusters. We have implemented these methods on NSF (National Science Foundation) XSEDE (Extreme Science and Engineering Discovery Environment) clusters and BOINC (Berkeley Open Infrastructure for Network Computing) distributed computing networks at Temple University and Brooklyn College at CUNY (the City University of New York). They are also being implemented on the IBM World Community Grid. To illustrate the methods, we have performed extensive (more than 60 ms in aggregate) simulations for the beta-cyclodextrin-heptanoate host-guest system in the context of one- and two-dimensional ASyncRE, and we used the results to estimate absolute binding free energies using the binding energy distribution analysis method. We propose ways to improve the efficiency of REMD simulations: these include increasing the number of exchanges attempted after a specified molecular dynamics (MD) period up to the fast exchange limit and/or adjusting the MD period to allow sufficient internal relaxation within each thermodynamic state. Although ASyncRE simulations generally require long MD periods (>picoseconds) per replica exchange cycle to minimize the overhead imposed by heterogeneous computing networks, we found that it is possible to reach an efficiency similar to conventional synchronous REMD, by optimizing the combination of the MD period and the number of exchanges attempted per cycle.
authors.affiliation: Center for Biophysics and Computational Biology, Department of Chemistry and Institute for Computational Molecular Science, Temple University, Philadelphia, 19122.
authors.forename: Junchao
authors.initials: J
authors.lastname: Xia
authors.affiliation: Center for Biophysics and Computational Biology, Department of Chemistry and Institute for Computational Molecular Science, Temple University, Philadelphia, 19122.|Department of Physics & Astronomy, Rutgers University, Piscataway, New Jersey, 08854.
authors.forename: William F
authors.initials: WF
authors.lastname: Flynn
authors.affiliation: Department of Chemistry, CUNY Brooklyn College, Brooklyn, New York, 11210.
authors.forename: Emilio
authors.initials: E
authors.lastname: Gallicchio
authors.affiliation: Center for Biophysics and Computational Biology, Department of Chemistry and Institute for Computational Molecular Science, Temple University, Philadelphia, 19122.
authors.forename: Bin W
authors.initials: BW
authors.lastname: Zhang
authors.affiliation: Center for Biophysics and Computational Biology, Department of Chemistry and Institute for Computational Molecular Science, Temple University, Philadelphia, 19122.
authors.forename: Peng
authors.initials: P
authors.lastname: He
authors.affiliation: Department of Statistics, Rutgers University, Piscataway, New Jersey, 08854.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Center for Biophysics and Computational Biology, Department of Chemistry and Institute for Computational Molecular Science, Temple University, Philadelphia, 19122.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Levy
mesh_terms: D000465:Algorithms; D006537:Heptanoates / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D013816:Thermodynamics; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D006537:Heptanoates; D047392:beta-Cyclodextrins; C031215:betadex
keywords: asynchronous replica exchange; binding energy distribution analysis method; distributed computing network; efficiency analysis; host-guest system; molecular dynamics