期刊
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
卷 8, 期 11, 页码 4672-4680出版社
AMER CHEMICAL SOC
DOI: 10.1021/ct300468g
关键词
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资金
- National Science Foundation [MCB-0920261]
- Computational Postdoctoral Fellowship of Argonne Leadership Computing Facility (ALCF)
- Early Science Postdoctoral Fellowship for Blue Gene/Q of ALCF
- Office of Science of the U.S. Department of Energy [DE-AC02-06CH11357]
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [920261] Funding Source: National Science Foundation
An extremely scalable computational strategy is described for calculations of the potential of mean force (PMF) in multidimensions on massively distributed supercomputers. The approach involves coupling thousands of umbrella sampling (US) simulation windows distributed to cover the space of order parameters with a Hamiltonian molecular dynamics replica exchange (H-REMD) algorithm to enhance the sampling of each simulation. In the present application, US/H-REMD is carried out in,a two-dimensional (2D) space and exchanges are attempted alternatively along the two axes corresponding to the two order parameters. The US/H-REMD strategy is implemented on the basis of parallel/parallel multiple copy protocol at the MPI level, and therefore can fully exploit computing power of large-scale supercomputers. Here the novel technique is illustrated using the leadership supercomputer IBM Blue Gene/P with an application to a typical biomolecular calculation of general interest, namely the binding of calcium ions to the small protein Calbindin D-9k. The free energy landscape associated with two order parameters, the distance between the ion and its binding pocket and the root-mean-square deviation (rmsd) of the binding pocket relative the crystal structure, was calculated using the US/H-REMD method. The results are then used to estimate the absolute binding free energy of calcium ion to Calbindin D-9k. The tests demonstrate that the 2D US/H-REMD scheme greatly accelerates the configurational sampling of the binding pocket, thereby improving the convergence of the potential of mean force calculation.
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