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.

中文翻译：

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复制交换高斯加速分子动力学：改进的增强采样和自由能计算

通过添加谐波升压势来平滑系统势能表面，高斯加速分子动力学 (GaMD) 无需预定义反应坐标即可提供增强的生物分子采样和自由能计算。这项工作通过将GaMD与副本交换算法相结合，继续提高GaMD的加速能力和能量重新加权。提出了副本交换 GaMD (rex-GaMD) 的两个版本：力常数 rex-GaMD 和阈值能量 rex-GaMD。在力常数 rex-GaMD 的模拟过程中，可以在具有固定阈值能量的不同谐波力常数的副本之间交换升压电势。然而，阈值能量rex-GaMD算法倾向于在下限和上限之间切换阈值能量，以产生不同水平的升压潜力。对丙氨酸二肽、chignolin和HIV蛋白酶等三个模型系统的测试模拟表明，通过不断交换增强电位，rex-GaMD模拟不仅增强了系统的构象转变，而且缩小了系统的分布宽度。所应用的升压潜力可用于精确的能量重新加权，以恢复生物分子自由能分布。