论文标题
Gromacs用非偶然性变化的中间体实施自由能计算
GROMACS Implementation of Free Energy Calculations with Non-Pairwise Variationally Derived Intermediates
论文作者
论文摘要
自由能中的梯度是物理和生化系统的驱动力。为了以高精度预测自由能差，分子动力学（MD）和其他基于原子性哈密顿量的方法在中间热力学状态下进行采样模拟，这些状态桥接了两个感兴趣的状态（“炼金术转化”）之间的构型空间密度。对于不相关的采样，最近衍生的中间体（VI）方法可产生最佳精度。 VI中间体的形式从根本上与常规的形式不同，因为它们是非双向的，即，中间状态中粒子上的总力不能分为周围粒子的加性贡献。在这项工作中，我们将VI的实现在广泛使用的Gromacs MD软件包（2020，版本1）中。此外，开发了VI的变体，避免了用于消失颗粒的数值不稳定性。该实施允许在文献中使用以前的非对势形式，迄今为止，gromacs尚未获得。提供了溶剂化自由能计算的示例案例及其准确性评估。
Gradients in free energies are the driving forces of physical and biochemical systems. To predict free energy differences with high accuracy, Molecular Dynamics (MD) and other methods based on atomistic Hamiltonians conduct sampling simulations in intermediate thermodynamic states that bridge the configuration space densities between two states of interest ('alchemical transformations'). For uncorrelated sampling, the recent Variationally derived Intermediates (VI) method yields optimal accuracy. The form of the VI intermediates differs fundamentally from conventional ones in that they are non-pairwise, i.e., the total force on a particle in an intermediate states cannot be split into additive contributions from the surrounding particles. In this work, we describe the implementation of VI into the widely used GROMACS MD software package (2020, version 1). Furthermore, a variant of VI is developed that avoids numerical instabilities for vanishing particles. The implementation allows the use of previous non-pairwise potential forms in the literature, which have so far not been available in GROMACS. Example cases on the calculation of solvation free energies, and accuracy assessments thereof, are provided.
