Shen Hujun, Czaplewski Cezary, Liwo Adam, Scheraga Harold A
Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853.
J Chem Theory Comput. 2008 Aug 1;4(8):1386-1400. doi: 10.1021/ct800063d.
The kinetic-trapping problem in simulating protein folding can be overcome by using a Replica Exchange Method (REM). However, in implementing REM in molecular dynamics simulations, synchronization between processors on parallel computers is required, and communication between processors limits its ability to sample conformational space in a complex system efficiently. To minimize communication between processors during the simulation, a Serial Replica Exchange Method (SREM) has been proposed recently by Hagan et al. (J. Phys. Chem. B2007, 111, 1416-1423). Here, we report the implementation of this new SREM algorithm with our physics-based united-residue (UNRES) force field. The method has been tested on the protein 1E0L with a temperature-independent UNRES force field and on terminally blocked deca-alanine (Ala(10)) and 1GAB with the recently introduced temperature-dependent UNRES force field. With the temperature-independent force field, SREM reproduces the results of REM but is more efficient in terms of wall-clock time and scales better on distributed-memory machines. However, exact application of SREM to the temperature-dependent UNRES algorithm requires the determination of a four-dimensional distribution of UNRES energy components instead of a one-dimensional energy distribution for each temperature, which is prohibitively expensive. Hence, we assumed that the temperature dependence of the force field can be ignored for neighboring temperatures. This version of SREM worked for Ala(10) which is a simple system but failed to reproduce the thermodynamic results as well as regular REM on the more complex 1GAB protein. Hence, SREM can be applied to the temperature-independent but not to the temperature-dependent UNRES force field.
通过使用副本交换方法（REM）可以克服模拟蛋白质折叠过程中的动力学捕获问题。然而，在分子动力学模拟中实现REM时，并行计算机上的处理器之间需要同步，并且处理器之间的通信限制了其在复杂系统中高效采样构象空间的能力。为了在模拟过程中最小化处理器之间的通信，Hagan等人（《物理化学杂志B》2007年，111卷，1416 - 1423页）最近提出了一种串行副本交换方法（SREM）。在此，我们报告了这种新的SREM算法与基于物理的统一残基（UNRES）力场的实现。该方法已在具有与温度无关的UNRES力场的蛋白质1E0L上进行了测试，并在末端封闭的十肽丙氨酸（Ala(10)）以及具有最近引入的与温度相关的UNRES力场的1GAB上进行了测试。对于与温度无关的力场，SREM重现了REM的结果，但在挂钟时间方面更高效，并且在分布式内存机器上扩展性更好。然而，将SREM精确应用于与温度相关的UNRES算法需要确定UNRES能量分量的四维分布，而不是每个温度下的一维能量分布，这成本过高。因此，我们假设相邻温度下力场的温度依赖性可以忽略。这种版本的SREM适用于简单系统Ala(10)，但在更复杂的1GAB蛋白质上未能重现热力学结果以及常规REM。因此，SREM可应用于与温度无关的UNRES力场，但不适用于与温度相关的UNRES力场。
