Rapid estimation of hydration thermodynamics of macromolecular regions.

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TitleRapid estimation of hydration thermodynamics of macromolecular regions.
Publication TypeJournal Article
Year of Publication2013
AuthorsE Raman, P, Mackerell, AD
JournalJ Chem Phys
Volume139
Issue5
Pagination055105
Date Published2013 Aug 07
ISSN1089-7690
KeywordsMacromolecular Substances, Molecular Dynamics Simulation, Monte Carlo Method, Thermodynamics, Water
Abstract

This work describes a novel protocol to efficiently calculate the local free energy of hydration of specific regions in macromolecules. The method employs Monte Carlo simulations in the grand canonical ensemble to generate water configurations in a selected spherical region in the macromolecule. Excess energy and entropy of hydration are calculated by analyzing the water configurational distributions following the recently published grid inhomogeneous solvation theory method [C. N. Nguyen, T. K. Young, and M. K. Gilson, J. Chem. Phys. 137, 044101 (2012)]. Our method involves the approximations of treating the macromolecule and distant solvent as rigid and performing calculations on multiple such conformations to account for conformational diversity. These approximations are tested against water configurations obtained from a molecular dynamics simulation. The method is validated by predicting the number and location of water molecules in 5 pockets in the protein Interleukin-1β for which experimental water occupancy data are available. Free energy values are validated against decoupling free energy perturbation calculations. The results indicate that the approximations used in the method enable efficient prediction of free energies of water displacement.

DOI10.1063/1.4817344
Alternate JournalJ Chem Phys
PubMed ID23927290
PubMed Central IDPMC3751957
Grant ListR01 AI080968 / AI / NIAID NIH HHS / United States
R01 CA107331 / CA / NCI NIH HHS / United States
AI080968 / AI / NIAID NIH HHS / United States
CA107331 / CA / NCI NIH HHS / United States