Conformational sampling via a self-regulating effective energy surface
Conformational sampling via a self-regulating effective energy surface
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DOI：
10.1063/1.2171194
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发表时间：
2006-05-07
影响因子：
4.4
通讯作者：
Karplus, M
中科院分区：
文献类型：
--
作者：
Bitetti-Putzer, R;Dinner, AR;Karplus, M
对具有粗糙能面复杂系统的相空间进行有效采样的难度是众所周知的。该问题的典型解决方案涉及加速跨越障碍，但此类方法通常存在次要问题，即所感兴趣的低能态没有充分采样，除非搜索算法的参数随着系统的发展而修改。提出了一种改进采样的方法，特别强调了对系统热力学贡献最大的低能构象。本文提出的算法对最小值的细节进行采样，同时很容易克服障碍。这是通过引入一个依赖于系统当前状态的自调节采样变量来实现的。引入系统的两个副本，并将采样变量视为与物理系统耦合的粒子。用一个简单的模型系统说明了该方法，并将其应用于蛋白质-配体复合物中垒穿越的实际例子。
The difficulty of efficiently sampling the phase space of complex systems with rough energy surfaces is well known. Typical solutions to the problem involve accelerating the crossing of barriers, but such methods often have the secondary problem that the low-energy states of interest are inadequately sampled, unless the parameters of the search algorithm are modified as the system evolves. A method is presented to improve the sampling with particular emphasis on the low-energy conformations, which make the most important contributions to the thermodynamics of the system. The algorithm proposed here samples the details of the minima, while easily surmounting barriers. This is achieved by introducing a self-regulating sampling variable which depends on the current state of the system. Two replicas of the system are introduced and the sampling variable is treated as a particle coupled to the physical system. The method is illustrated with a simple model system and is applied to the realistic example of barrier crossing in a protein-ligand complex.