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    Shuwei Jin, Jia-Ning Wang, Yuanfei Xue, Pengfei Li, Ye Mei. Selectivity of Parvalbumin B Protein Binding to Ca$ ^{\textbf{2+}} $ and Mg$ ^{\textbf{2+}} $ at an $ \mathit{{Ab}} $ $ \mathit{{Initio}} $ QM/MM Level Using the Reference-Potential Method[J]. Chinese Journal of Chemical Physics , 2021, 34(6): 741-750. DOI: 10.1063/1674-0068/cjcp2109176
    Citation: Shuwei Jin, Jia-Ning Wang, Yuanfei Xue, Pengfei Li, Ye Mei. Selectivity of Parvalbumin B Protein Binding to Ca$ ^{\textbf{2+}} $ and Mg$ ^{\textbf{2+}} $ at an $ \mathit{{Ab}} $ $ \mathit{{Initio}} $ QM/MM Level Using the Reference-Potential Method[J]. Chinese Journal of Chemical Physics , 2021, 34(6): 741-750. DOI: 10.1063/1674-0068/cjcp2109176
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    Selectivity of Parvalbumin B Protein Binding to Ca ^\textbf2+ and Mg ^\textbf2+ at an \mathitAb \mathitInitio QM/MM Level Using the Reference-Potential Method

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      • Abstract
    • Ion selectivity in protein binding sites is of great significance to biological functions. Although additive force fields have been successfully applied to various protein-related studies, it is difficult to well capture the subtle metal-protein interaction for the prediction of ion selectivity, due to the remarkable polarization and charge transfer effect between the metals and the surrounding residues. Quantum mechanics-based methods are well-suited for dealing with these systems, but they are too costly to apply in a direct manner. In this work, the reference-potential method (RPM) was used to measure the selectivity for calcium and magnesium cations in the binding pocket of parvalbumin B protein by calculating the free energy change associated with this substitution reaction at an ab initio quantum mechanics/molecular mechanics (QM/MM) level. The alchemical transformations were performed at the molecular mechanics level, and the relative binding free energy was then corrected to the QM/MM level via thermodynamic perturbation. In this way, the free energy change at the QM/MM level for the substitution reaction was obtained without running the QM/MM simulations, thus remarkably enhancing the efficiency. In the reweighting process, we found that the selection of the QM region greatly affects the accuracy of the QM/MM method. In particular, the charge transfer effect on the free energy change of a reaction cannot be neglected.
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