Perspective on free-energy perturbation calculations for chemical equilibria
Perspective on free-energy perturbation calculations for chemical equilibria
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DOI：
10.1021/ct800011m
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发表时间：
2008-06-01
影响因子：
5.5
通讯作者：
Thomas, Laura L.
中科院分区：
文献类型：
--
作者：
Jorgensen, William L.;Thomas, Laura L.
背景自由能变化的计算对于反应途径和化学平衡的热力学表征至关重要。传统的方法，自由能微扰（FEP）和热力学积分（TI），是基于柯克伍德在流体系统积分方程研究中引入连续耦合参数而得出的。 1, 2 Zwanzig 后来的工作进一步推进了自由能微扰理论的数学形式，3 与分子动力学和蒙特卡罗采样技术相结合，已成为计算自由能差异的主要方法。 2, 4, 5 一些应用包括计算溶剂化的相对自由能、相对 pKa 值、构象平衡的介质效应、主客体结合亲和力以及有机和生化反应的自由能表面。 Zwanzig 在其 1954 年的论文 3 中提出了自由能扰动理论，该理论将系统的初始（参考）状态和最终（目标）状态之间的自由能差与通过初始状态采样评估的能量差函数平均值联系起来（方程 1）。
BackgroundThe calculation of free energy changes is fundamental for the thermodynamic characterization of reaction pathways and chemical equilibria. The conventional approaches, free energy perturbation (FEP) and thermodynamic integration (TI), were predicated on Kirkwood’s introduction of the continuous coupling parameter in his integral equation studies of fluid systems. 1, 2 Later work by Zwanzig further advanced the mathematical formalism of free energy perturbation theory, 3 and this, in conjunction with molecular dynamics and Monte Carlo sampling techniques, has become a principal approach for calculating free-energy differences. 2, 4, 5 Some applications have included computation of relative free energies of solvation, relative pKa values, medium-effects on conformational equilibria, host-guest binding affinities, and free-energy surfaces for organic and biochemical reactions. Free energy perturbation theory, as presented by Zwanzig in his 1954 paper, 3 relates the free energy difference between an initial (reference) and a final (target) state of a system to an average of a function of their energy difference evaluated by sampling for the initial state (eq 1).