Khavrutskii Ilja V, Wallqvist Anders
Biotechnology HPC Software Applications Institute, Telemedicine and Advanced Technology Research Center, US Army Medical Research and Materiel Command, Fort Detrick, MD 21702.
J Chem Theory Comput. 2010 Nov 9;6(11):3427-3441. doi: 10.1021/ct1003302.
This paper introduces an efficient single-topology variant of Thermodynamic Integration (TI) for computing relative transformation free energies in a series of molecules with respect to a single reference state. The presented TI variant that we refer to as Single-Reference TI (SR-TI) combines well-established molecular simulation methodologies into a practical computational tool. Augmented with Hamiltonian Replica Exchange (HREX), the SR-TI variant can deliver enhanced sampling in select degrees of freedom. The utility of the SR-TI variant is demonstrated in calculations of relative solvation free energies for a series of benzene derivatives with increasing complexity. Noteworthy, the SR-TI variant with the HREX option provides converged results in a challenging case of an amide molecule with a high (13-15 kcal/mol) barrier for internal cis/trans interconversion using simulation times of only 1 to 4 ns.
本文介绍了一种高效的热力学积分（TI）单拓扑变体，用于计算一系列分子相对于单个参考态的相对转化自由能。我们将提出的TI变体称为单参考TI（SR-TI），它将成熟的分子模拟方法整合为一种实用的计算工具。通过哈密顿量副本交换（HREX）增强后，SR-TI变体可以在选定的自由度上实现增强采样。在计算一系列复杂度不断增加的苯衍生物的相对溶剂化自由能时，展示了SR-TI变体的实用性。值得注意的是，带有HREX选项的SR-TI变体在一个具有高（13-15千卡/摩尔）内顺/反互变势垒的酰胺分子的具有挑战性的案例中，仅使用1至4纳秒的模拟时间就提供了收敛结果。
