Examining the limits of time reweighting and Kramers' rate theory to obtain correct kinetics from accelerated molecular dynamics.
Examining the limits of time reweighting and Kramers' rate theory to obtain correct kinetics from accelerated molecular dynamics.
复制标题
检查时间重新加权和克莱默速率理论的限制，从加速分子动力学中获得正确的动力学。
DOI：
10.1063/1.3432761
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
D. Hamelberg
中科院分区：
文献类型：
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作者：
Yao Xin;U. Doshi;D. Hamelberg
加速分子动力学模拟通常用于恢复与生物分子系统的原始势能景观相对应的正确的正则概率分布。然而，在从生物分子系统的加速分子动力学获得真实动力学速率方面，基于过渡态理论的时间重新加权的限制不太明显。在这里，我们研究这个问题，通过研究的顺反异构化的肽ω键的加速分子动力学。我们发现，时间重新加权是有效的，获得真正的动力学时，原始的潜力是不改变过渡态区域，如预期的。当原始的潜在景观被修改，使得所施加的升压电位改变过渡态区域时，时间重新加权不能再现正确的动力学，并且重新加权的速率比真实速率慢得多。通过采用Kramers速率理论的过阻尼极限，我们成功地恢复了正确的动力学，而不管过渡态区域是否被修改。此外，我们测试的有效性的加速权重因子从路径积分形式主义获得正确的动力学顺反异构化。研究发现，这种权重因子的公式不适合长时间尺度的过程，例如具有高能垒的顺反异构化。
Accelerated molecular dynamics simulations are routinely being used to recover the correct canonical probability distributions corresponding to the original potential energy landscape of biomolecular systems. However, the limits of time reweighting, based on transition state theory, in obtaining true kinetic rates from accelerated molecular dynamics for biomolecular systems are less obvious. Here, we investigate this issue by studying the kinetics of cis-trans isomerization of peptidic omega bond by accelerated molecular dynamics. We find that time reweighting is valid for obtaining true kinetics when the original potential is not altered at the transition state regions, as expected. When the original potential landscape is modified such that the applied boost potential alters the transition state regions, time reweighting fails to reproduce correct kinetics and the reweighted rate is much slower than the true rate. By adopting the overdamped limit of Kramers' rate theory, we are successful in recovering correct kinetics irrespective of whether or not the transition state regions are modified. Furthermore, we tested the validity of the acceleration weight factor from the path integral formalism for obtaining the correct kinetics of cis-trans isomerization. It was found that this formulation of the weight factor is not suitable for long time scale processes such as cis-trans isomerization with high energy barriers.