When it rains it pours! Three papers of ours have been just accepted for publication.
Emilio Gallicchio, Junchao Xia, William F Flynn, Baofeng Zhang, Sade Samlalsingh, Ahmet Mentes, Ronald M Levy
Asynchronous Replica Exchange Software for Grid and Heterogeneous Computing
Computer Physics Communications, in press (2015)
Abstract. Parallel replica exchange sampling is an extended ensemble technique often used to accelerate the exploration of the conformational ensemble of atomistic molecular simulations of chemical systems. Inter-process communication and coordination requirements have historically discouraged the deployment of replica exchange on distributed and heterogeneous resources. Here we describe the architecture of a software (named ASyncRE) for performing asynchronous replica exchange molecular simulations on volunteered computing grids and heterogeneous high performance clusters. The asynchronous replica exchange algorithm on which the software is based avoids centralized synchronization steps and the need for direct communication between remote processes. It allows molecular dynamics threads to progress at different rates and enables parameter exchanges among arbitrary sets of replicas independently from other replicas. ASyncRE is written in Python following a modular design conducive to extensions to various replica exchange schemes and molecular dynamics engines. Applications of the software for the modeling of association equilibria of supramolecular and macromolecular complexes on BOINC campus computational grids and on the CPU/MIC heterogeneous hardware of the XSEDE Stampede supercomputer are illustrated. They show the ability of ASyncRE to utilize large grids of desktop computers running the Windows, MacOS, and/or Linux operating systems as well as collections of high performance heterogeneous hardware devices.
Junchao Xia, William F. Flynn, Emilio Gallicchio, Bin W. Zhang, Peng He, Zhiqiang Tan, Ronald M. Levy.
Large Scale Asynchronous and Distributed Multi-Dimensional Replica Exchange Molecular Simulations and Efficiency Analysis
J. Comp. Chem, in press (2015).
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 XSEDE clusters and BOINC distributed computing networks at Temple University, and Brooklyn College at CUNY. They are also being implemented on the IBM World Community Grid. To illustrate the methods we have performed extensive (more than 60 microseconds 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 (BEDAM). We propose ways to improve the efficiency of REMD simulations: these include increasing the number of exchanges attempted after a specified 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.
Lauren Wickstrom, Nanjie Deng, Peng He, Ahmet Mentes ,Crystal Nguyen, Michael K. Gilson, Tom Kurtzman, Emilio Gallicchio, and Ronald M. Levy
Parameterization of an effective potential for protein-ligand binding from host-guest affinity data
J. Molecular Recognition, in press (2015)
Abstract. Force field accuracy is still one of the “stalemates” in biomolecular modeling. Model systems with high quality experimental data are valuable instruments for the validation and improvement of effective potentials. With respect to protein-ligand binding, organic host-guest complexes have long served as models for both experimental and computational studies due to the abundance of binding affinity data available for such systems. Binding affinity data collected for cyclodextrin (CD) inclusion complexes, a popular model for molecular recognition, is potentially a more reliable resource for tuning energy parameters than hydration free energy measurements. Convergence of binding free energy calculations on CD host-guest systems can also be obtained rapidly, thus offering the opportunity to assess the robustness of these parameters. In this work, we demonstrate how implicit solvent parameters can be developed using binding affinity experimental data and the binding energy distribution analysis method (BEDAM) and validated using Grid Inhomogeneous Solvation Theory analysis. These new solvation parameters were used to study protein-ligand binding in two drug targets against the HIV-1 virus, and improved the agreement between the calculated and the experimental binding affinities. This work illustrates how benchmark sets of high quality experimental binding affinity data and physics-based binding free energy models can be used to evaluate and optimize force fields for protein-ligand systems.
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