Department of Chemistry and The Center for Biotechnology and Drug Design, Georgia State University, Atlanta, Georgia 30302-4098, USA.
J Chem Phys. 2010 Jun 14;132(22):224101. doi: 10.1063/1.3432761.
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.
加速分子动力学模拟通常用于恢复与生物分子系统原始势能景观相对应的正确正则概率分布。然而，基于过渡态理论的时间重加权在从加速分子动力学中获得生物分子系统的真实动力学速率方面的限制不太明显。在这里，我们通过研究加速分子动力学中肽ω键顺反异构化的动力学来研究这个问题。我们发现，当原始势能在过渡态区域没有改变时，时间重加权适用于获得真实的动力学，这是预期的。当原始势能景观被修改使得施加的提升势能改变过渡态区域时，时间重加权无法再现正确的动力学，并且重加权速率比真实速率慢得多。通过采用克拉默斯速率理论的过阻尼极限，我们成功地恢复了正确的动力学，无论过渡态区域是否被修改。此外，我们还测试了路径积分形式主义中加速权重因子用于获得顺反异构化正确动力学的有效性。结果发现，这种权重因子的表述不适用于具有高能量势垒的顺反异构化等长时标过程。
