Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Okazaki, Aichi, Japan.
Institute for Molecular Science, National Institutes of Natural Sciences, Okazaki, Aichi, Japan.
Methods Mol Biol. 2022;2340:197-220. doi: 10.1007/978-1-0716-1546-1_10.
Protein aggregates are associated with more than 40 serious human diseases. To understand the formation mechanism of protein aggregates at atomic level, all-atom molecular dynamics (MD) simulation is a powerful computational tool. In this chapter, we review the all-atom MD simulation methods that are useful for study on the protein aggregation. We first explain conventional MD simulation methods in physical statistical ensembles, such as the canonical and isothermal-isobaric ensembles. We then describe the generalized-ensemble algorithms such as replica-exchange and replica-permutation MD methods. These methods can overcome a difficulty, in which simulations tend to get trapped in local-minimum free-energy states. Finally we explain the nonequilibrium MD method. Some simulation results based on these methods are also presented.
蛋白质聚集体与 40 多种严重的人类疾病有关。为了在原子水平上理解蛋白质聚集体的形成机制，全原子分子动力学（MD）模拟是一种强大的计算工具。在本章中，我们回顾了对蛋白质聚集研究有用的全原子 MD 模拟方法。我们首先解释了物理统计系综中的传统 MD 模拟方法，例如正则和等温等压系综。然后，我们描述了广义系综算法，例如复制交换和复制置换 MD 方法。这些方法可以克服模拟倾向于陷入局部最小自由能状态的困难。最后，我们解释了非平衡 MD 方法。还给出了基于这些方法的一些模拟结果。
