J Chem Theory Comput. 2018 Apr 10;14(4):1853-1864. doi: 10.1021/acs.jctc.7b01226. Epub 2018 Mar 12.
Through adding a harmonic boost potential to smooth the system potential energy surface, Gaussian accelerated molecular dynamics (GaMD) provides enhanced sampling and free energy calculation of biomolecules without the need of predefined reaction coordinates. This work continues to improve the acceleration power and energy reweighting of the GaMD by combining the GaMD with replica exchange algorithms. Two versions of replica exchange GaMD (rex-GaMD) are presented: force constant rex-GaMD and threshold energy rex-GaMD. During simulations of force constant rex-GaMD, the boost potential can be exchanged between replicas of different harmonic force constants with fixed threshold energy. However, the algorithm of threshold energy rex-GaMD tends to switch the threshold energy between lower and upper bounds for generating different levels of boost potential. Testing simulations on three model systems, including the alanine dipeptide, chignolin, and HIV protease, demonstrate that through continuous exchanges of the boost potential, the rex-GaMD simulations not only enhance the conformational transitions of the systems but also narrow down the distribution width of the applied boost potential for accurate energetic reweighting to recover biomolecular free energy profiles.
通过在平滑系统势能表面时添加谐波提升势，高斯加速分子动力学（GaMD）为生物分子提供了增强的采样和自由能计算，而无需预定义反应坐标。这项工作通过将 GaMD 与 replica exchange 算法相结合，继续提高 GaMD 的加速能力和能量重新加权能力。本文提出了两种 replica exchange GaMD（rex-GaMD）版本：力常数 rex-GaMD 和阈值能量 rex-GaMD。在力常数 rex-GaMD 的模拟中，可以在具有固定阈值能量的不同谐波力常数 replica 之间交换提升势。然而，阈值能量 rex-GaMD 的算法倾向于在较低和较高的阈值能量之间切换，以产生不同水平的提升势。在三个模型系统（包括丙氨酸二肽、chignolin 和 HIV 蛋白酶）上的测试模拟表明，通过不断交换提升势，rex-GaMD 模拟不仅增强了系统的构象转变，而且还缩小了应用提升势的分布宽度，以便进行准确的能量重新加权，以恢复生物分子自由能分布。
