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Zhang BW , Cui D , Matubayasi N , Levy RM
The Excess Chemical Potential of Water at the Interface with a Protein from End Point Simulations
J Phys Chem B. 2018 Apr 23;122(17) :4700-4707
PMID: 29634902    PMCID: PMC5939383    URL: https://www.ncbi.nlm.nih.gov/pubmed/29634902
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Abstract
We use end point simulations to estimate the excess chemical potential of water in the homogeneous liquid and at the interface with a protein in solution. When the pure liquid is taken as the reference, the excess chemical potential of interfacial water is the difference between the solvation free energy of a water molecule at the interface and in the bulk. Using the homogeneous liquid as an example, we show that the solvation free energy for growing a water molecule can be estimated by applying UWHAM to the simulation data generated from the initial and final states (i.e., "the end points") instead of multistate free energy perturbation simulations because of the possible overlaps of the configurations sampled at the end points. Then end point simulations are used to estimate the solvation free energy of water at the interface with a protein in solution. The estimate of the solvation free energy at the interface from two simulations at the end points agrees with the benchmark using 32 states within a 95% confidence interval for most interfacial locations. The ability to accurately estimate the excess chemical potential of water from end point simulations facilitates the statistical thermodynamic analysis of diverse interfacial phenomena. Our focus is on analyzing the excess chemical potential of water at protein receptor binding sites with the goal of using this information to assist in the design of tight binding ligands.
Notes
1520-5207 Zhang, Bin W ORCID: http://orcid.org/0000-0003-3007-4900 Cui, Di ORCID: http://orcid.org/0000-0001-8609-8472 Matubayasi, Nobuyuki ORCID: http://orcid.org/0000-0001-7176-441X Levy, Ronald M ORCID: http://orcid.org/0000-0001-8696-5177 R01 GM030580/GM/NIGMS NIH HHS/United States S10 OD020095/OD/NIH HHS/United States Journal Article United States J Phys Chem B. 2018 Apr 23. doi: 10.1021/acs.jpcb.8b02666.