Gaussian Accelerated Molecular Dynamics: Unconstrained Enhanced Sampling and Free Energy Calculation.
Gaussian Accelerated Molecular Dynamics: Unconstrained Enhanced Sampling and Free Energy Calculation.
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DOI：
10.1021/acs.jctc.5b00436
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发表时间：
2015-08-11
影响因子：
5.5
通讯作者：
McCammon JA
中科院分区：
文献类型：
--
作者：
Miao Y;Feher VA;McCammon JA
提出了一种用于生物分子同时增强采样和自由能计算的高斯加速分子动力学（GaMD）方法。通过构造一个服从高斯分布的升压势，利用二阶累积量展开实现了GaMD模拟的精确重加权。在这里，GaMD证明了三个生物分子模型系统：丙氨酸二肽，chignolin折叠，和配体结合的T4-溶菌酶。无需设置预定义的反应坐标，GaMD可以对这些生物分子进行无约束的增强采样。此外，从GaMD模拟的重新加权获得的自由能分布使我们能够识别不同的低能量状态的生物分子和定量表征的蛋白质折叠和配体结合途径。
A Gaussian accelerated molecular dynamics (GaMD) approach for simultaneous enhanced sampling and free energy calculation of biomolecules is presented. By constructing a boost potential that follows Gaussian distribution, accurate reweighting of the GaMD simulations is achieved using cumulant expansion to the second order. Here, GaMD is demonstrated on three biomolecular model systems: alanine dipeptide, chignolin folding, and ligand binding to the T4-lysozyme. Without the need to set predefined reaction coordinates, GaMD enables unconstrained enhanced sampling of these biomolecules. Furthermore, the free energy profiles obtained from reweighting of the GaMD simulations allow us to identify distinct low-energy states of the biomolecules and characterize the protein-folding and ligand-binding pathways quantitatively.