Enhanced sampling techniques in molecular dynamics simulations of biological systems.
Enhanced sampling techniques in molecular dynamics simulations of biological systems.
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DOI：
10.1016/j.bbagen.2014.10.019
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发表时间：
2015-05
影响因子：
3
通讯作者：
Schulten, Klaus
中科院分区：
文献类型：
--
作者：
Bernardi, Rafael C.;Melo, Marcelo C. R.;Schulten, Klaus
关键词：
分子动力学已经成为一种重要的研究方法，涵盖了数百万个原子级别的系统。然而，抽样不足往往限制了它的应用。这种限制是由于粗糙的能量环境造成的，许多局部极小值被控制生物分子运动的高能势垒隔开。在过去的几十年里，已经发展了解决采样问题的方法，如复制交换分子动力学、元动力学和模拟退火法。在这里，我们对这些采样方法进行了概述，试图阐明应根据所研究的系统属性的类型选择哪种方法。对广泛的生物系统采用了改进的采样方法，选择合适的方法与系统的生物和物理特性，特别是系统的大小有关。虽然元动力学和复制交换分子动力学是研究生物分子动力学最常用的抽样方法，但模拟退火法非常适合描述非常灵活的系统。长期以来，退火法的使用仅限于对小分子蛋白质的模拟；然而，广义模拟退火法的一个变种，可以以相对较低的计算成本应用于大分子复合体。分子动力学轨迹通常不会到达所有相关的构象亚态，例如那些与生物功能相关的构象亚态，这一问题可以通过采用增强的采样算法来解决。
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.
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