Repulsive Soft-Core Potentials for Efficient Alchemical Free Energy Calculations.,Journal of Chemical Theory and Computation

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Repulsive Soft-Core Potentials for Efficient Alchemical Free Energy Calculations.
Journal of Chemical Theory and Computation ( IF 5.7 ) Pub Date : 2020-06-19 , DOI: 10.1021/acs.jctc.0c00163
Yaozong Li _{1,

2} , Kwangho Nam _{1,

3}

Affiliation

In alchemical free energy (FE) simulations, annihilation and creation of atoms are generally achieved with the soft-core potential that shifts the interparticle separations. While this soft-core potential eliminates the numerical instability occurring near the two end states of the transformation, it makes the hybrid Hamiltonian vary nonlinearly with respect to the parameter λ, which interpolates between the Hamiltonians representing the two end states. This complicates FE estimation by Bennett acceptance ratio (BAR), free energy perturbation (FEP), and thermodynamic integration (TI) methods, thus reducing their calculation efficiency. In this work, we develop a new type of repulsive soft-core potential, called Gaussian soft-core (GSC) potential, with two parameters controlling its maximum and width. The main advantage of this potential is the linearity of the hybrid Hamiltonian with respect to λ, thus permitting the direct application of BAR, FEP, TI, and other variant FE methods. The accuracy and efficiency of the GSC potential are demonstrated by comparing the free energies of annihilation determined for 13 small molecules and an alchemical mutation of a protein side chain. In addition, in combination with a TI integrand (∂H/∂λ) estimation strategy, we show that GSC can considerably reduce the number of λ simulations compared to the commonly used separation-shifted soft-core potential.

中文翻译：

用于有效炼金术自由能计算的排斥软核电势。

在炼金术自由能 (FE) 模拟中，原子的湮灭和创造通常是通过改变粒子间分离的软核势来实现的。虽然这种软核势消除了在转换的两个结束状态附近发生的数值不稳定性，但它使混合哈密顿量相对于参数 λ 非线性变化，该参数在代表两个结束状态的哈密顿量之间进行插值。这使通过 Bennett 接受比 (BAR)、自由能扰动 (FEP) 和热力学积分 (TI) 方法进行的有限元估计复杂化，从而降低了它们的计算效率。在这项工作中，我们开发了一种新型的排斥软核势，称为高斯软核 (GSC) 势，有两个参数控制其最大值和宽度。这种潜力的主要优点是混合哈密顿量相对于 λ 的线性，从而允许直接应用 BAR、FEP、TI 和其他变体 FE 方法。通过比较为 13 个小分子和蛋白质侧链的炼金术突变确定的湮灭自由能，证明了 GSC 电位的准确性和效率。此外，结合 TI 被积函数 (∂H /∂λ) 估计策略，我们表明与常用的分离移位软核潜力相比，GSC 可以显着减少 λ 模拟的数量。

更新日期：2020-08-11

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