Computing pKa Values with a Mixing Hamiltonian Quantum Mechanical/Molecular Mechanical Approach

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• 作者：Yang Liu ; Xiaoli Fan ; Yingdi Jin ; Xiangqian Hu ; Hao Hu
• 刊名：Journal of Chemical Theory and Computation
• 出版年：2013
• 出版时间：September 10, 2013
• 年：2013
• 卷：9
• 期：9
• 页码：4257-4265
• 全文大小：295K
• 年卷期：v.9,no.9(September 10, 2013)
• ISSN：1549-9626

文摘

Accurate computation of the pK_a value of a compound in solution is important but challenging. Here, a new mixing quantum mechanical/molecular mechanical (QM/MM) Hamiltonian method is developed to simulate the free-energy change associated with the protonation/deprotonation processes in solution. The mixing Hamiltonian method is designed for efficient quantum mechanical free-energy simulations by alchemically varying the nuclear potential, i.e., the nuclear charge of the transforming nucleus. In pK_a calculation, the charge on the proton is varied in fraction between 0 and 1, corresponding to the fully deprotonated and protonated states, respectively. Inspired by the mixing potential QM/MM free energy simulation method developed previously [H. Hu and W. T. Yang, J. Chem. Phys. 2005, 123, 041102], this method succeeds many advantages of a large class of 位-coupled free-energy simulation methods and the linear combination of atomic potential approach. Theory and technique details of this method, along with the calculation results of the pK_a of methanol and methanethiol molecules in aqueous solution, are reported. The results show satisfactory agreement with the experimental data.