title: Computation of Absolute Hydration and Binding Free Energy with Free Energy Perturbation Distributed Replica-Exchange Molecular Dynamics (FEP/REMD).
abstract: 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.
authors.affiliation: Biosciences Division, Argonne National Laboratory, 9700 South Cass Avenue, Building 221, Argonne, Illinois 60439, USACenter for Molecular Modeling, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia,Department of Biochemistry and Molecular Biology, Gordon Center for Integrative Science, University of Chicago, 929 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Milan
authors.initials: M
authors.lastname: Hodoscek
authors.forename: Benoît
authors.initials: B
authors.lastname: Roux