Bernardi Rafael C, Melo Marcelo C R, Schulten Klaus
Beckman Institute, University of Illinois, Urbana, IL 61801, USA.
Center for Biophysics and Computational Biology, University of Illinois, Urbana, IL 61801, USA.
Biochim Biophys Acta. 2015 May;1850(5):872-877. doi: 10.1016/j.bbagen.2014.10.019. Epub 2014 Oct 23.
Molecular dynamics has emerged as an important research methodology covering systems to the level of millions of atoms. However, insufficient sampling often limits its application. The limitation is due to rough energy landscapes, with many local minima separated by high-energy barriers, which govern the biomolecular motion.
In the past few decades methods have been developed that address the sampling problem, such as replica-exchange molecular dynamics, metadynamics and simulated annealing. Here we present an overview over theses sampling methods in an attempt to shed light on which should be selected depending on the type of system property studied.
Enhanced sampling methods have been employed for a broad range of biological systems and the choice of a suitable method is connected to biological and physical characteristics of the system, in particular system size. While metadynamics and replica-exchange molecular dynamics are the most adopted sampling methods to study biomolecular dynamics, simulated annealing is well suited to characterize very flexible systems. The use of annealing methods for a long time was restricted to simulation of small proteins; however, a variant of the method, generalized simulated annealing, can be employed at a relatively low computational cost to large macromolecular complexes.
Molecular dynamics trajectories frequently do not reach all relevant conformational substates, for example those connected with biological function, a problem that can be addressed by employing enhanced sampling algorithms. This article is part of a Special Issue entitled Recent developments of molecular dynamics.
分子动力学已成为一种重要的研究方法，可涵盖数百万原子水平的系统。然而，采样不足常常限制其应用。这种限制源于粗糙的能量景观，其中许多局部极小值被高能势垒隔开，这些势垒支配着生物分子的运动。
在过去几十年中，已开发出解决采样问题的方法，如副本交换分子动力学、元动力学和模拟退火。在此，我们对这些采样方法进行概述，试图阐明应根据所研究系统性质的类型选择哪种方法。
增强采样方法已应用于广泛的生物系统，合适方法的选择与系统的生物学和物理特征相关，特别是系统大小。虽然元动力学和副本交换分子动力学是研究生物分子动力学最常用的采样方法，但模拟退火非常适合表征非常灵活的系统。长期以来，退火方法的使用仅限于小蛋白质的模拟；然而，该方法的一个变体，广义模拟退火，可以以相对较低的计算成本应用于大型大分子复合物。
分子动力学轨迹常常无法到达所有相关的构象亚态，例如那些与生物学功能相关的亚态，这个问题可以通过采用增强采样算法来解决。本文是名为“分子动力学的最新发展”的特刊的一部分。
