General Quantum Alchemical Free Energy Simulations via Hamiltonian Interpolation.

IF 5.7 1区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Chemical Theory and Computation Pub Date : 2025-06-20 DOI:10.1021/acs.jctc.5c00682

Chenghan Li, Xing Zhang, Garnet Kin-Lic Chan

引用次数: 0

Abstract

We present an implementation of alchemical free energy simulations at the quantum mechanical level by directly interpolating the electronic Hamiltonian. The method is compatible with any level of electronic structure theory and requires only one quantum calculation for each molecular dynamics step in contrast to multiple energy evaluations that would be needed when interpolating the ground-state energies. We demonstrate the correctness and applicability of the technique by computing alchemical free energy changes of gas-phase molecules, with both nuclear and electron creation/annihilation. We also show an initial application to first-principles pK_a calculation for solvated molecules where we quantum mechanically annihilate a bonded proton.

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基于哈密顿插值的通用量子炼金术自由能模拟。

我们通过直接插入电子哈密顿量，在量子力学水平上实现了炼金术自由能的模拟。该方法与任何水平的电子结构理论兼容，并且每个分子动力学步骤只需要一个量子计算，而不是在插入基态能量时需要多次能量评估。我们通过计算具有核和电子产生/湮灭的气相分子的炼金术自由能变化来证明该技术的正确性和适用性。我们还展示了对溶剂化分子的第一性原理pKa计算的初步应用，其中我们量子力学地湮灭了键合质子。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Chemical Theory and Computation 化学-物理：原子、分子和化学物理

CiteScore

9.90

自引率

16.40%

发文量

568

审稿时长

1 months

期刊介绍： The Journal of Chemical Theory and Computation invites new and original contributions with the understanding that, if accepted, they will not be published elsewhere. Papers reporting new theories, methodology, and/or important applications in quantum electronic structure, molecular dynamics, and statistical mechanics are appropriate for submission to this Journal. Specific topics include advances in or applications of ab initio quantum mechanics, density functional theory, design and properties of new materials, surface science, Monte Carlo simulations, solvation models, QM/MM calculations, biomolecular structure prediction, and molecular dynamics in the broadest sense including gas-phase dynamics, ab initio dynamics, biomolecular dynamics, and protein folding. The Journal does not consider papers that are straightforward applications of known methods including DFT and molecular dynamics. The Journal favors submissions that include advances in theory or methodology with applications to compelling problems.