Replica-Exchange and Standard State Binding Free Energies with Grand Canonical Monte Carlo.

Autor:	Ross GA; Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center , New York, New York 10065, United States., Bruce Macdonald HE; Department of Chemistry, University of Southampton , Southampton, SO17 1BJ, United Kingdom., Cave-Ayland C; Department of Chemistry, University of Southampton , Southampton, SO17 1BJ, United Kingdom., Cabedo Martinez AI; Department of Chemistry, University of Southampton , Southampton, SO17 1BJ, United Kingdom., Essex JW; Department of Chemistry, University of Southampton , Southampton, SO17 1BJ, United Kingdom.
Jazyk:	angličtina
Zdroj:	Journal of chemical theory and computation [J Chem Theory Comput] 2017 Dec 12; Vol. 13 (12), pp. 6373-6381. Date of Electronic Publication: 2017 Nov 28.
DOI:	10.1021/acs.jctc.7b00738
Abstrakt:	The ability of grand canonical Monte Carlo (GCMC) to create and annihilate molecules in a given region greatly aids the identification of water sites and water binding free energies in protein cavities. However, acceptance rates without the application of biased moves can be low, resulting in large variations in the observed water occupancies. Here, we show that replica-exchange of the chemical potential significantly reduces the variance of the GCMC data. This improvement comes at a negligible increase in computational expense when simulations comprise of runs at different chemical potentials. Replica-exchange GCMC is also found to substantially increase the precision of water binding free energies as calculated with grand canonical integration, which has allowed us to address a missing standard state correction.
Databáze:	MEDLINE
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