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Computation of Absolute Hydration and Binding Free Energy with Free Energy Perturbation Distributed Replica-Exchange Molecular Dynamics (FEP/REMD)



Computation of Absolute Hydration and Binding Free Energy with Free Energy Perturbation Distributed Replica-Exchange Molecular Dynamics (FEP/REMD)



Journal of Chemical Theory and Computation 5(10): 2583-2588



Distributed Replica (REPDSTR) is a powerful parallelization technique enabling simulations of a group of replicas in a parallel/parallel fashion, where each replica is distributed to different nodes of a large cluster [Theor. Chem. Acc. 109: 140 (2003)]. Here, we use the framework provided by REPDSTR to combine a staged free energy perturbation protocol with different values of the thermodynamic coupling parameters with replica-exchange molecular dynamics (FEP/REMD. The structure of REPDSTR, which allows multiple parallel input/output (I/O), facilitates the treatment of replica-exchange to couple the N window simulations. As a result, each of the N synchronous window simulations benefit from the sampling carried out by the N-1 others. As illustrative examples of the FEP/REMD strategy, calculations of the absolute hydration and binding free energy of small molecules were performed using the biomolecular simulation program CHARMM adapted for the IBM Blue Gene/P platform. The computations show that a FEP/REMD strategy significantly improves the sampling and accelerate the convergence of absolute free energy computations.

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Accession: 052272713

Download citation: RISBibTeXText

PMID: 21857812

DOI: 10.1021/ct900223z


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