Computational Biology and Biological Physics, Lund University, Sölvegatan 14A, SE-223 62 Lund, Sweden.
J Chem Phys. 2011 Sep 28;135(12):125102. doi: 10.1063/1.3643328.
Flat-histogram techniques provide a powerful approach to the simulation of first-order-like phase transitions and are potentially very useful for protein studies. Here, we test this approach by implicit solvent all-atom Monte Carlo (MC) simulations of peptide aggregation, for a 7-residue fragment (GIINFEQ) [corrected] of the Cu/Zn superoxide dismutase 1 protein (SOD1). In simulations with 8 chains, we observe two distinct aggregated/non-aggregated phases. At the midpoint temperature, these phases coexist, separated by a free-energy barrier of height 2.7 k(B)T. We show that this system can be successfully studied by carefully implemented flat-histogram techniques. The frequency of barrier crossing, which is low in conventional canonical simulations, can be increased by turning to a two-step procedure based on the Wang-Landau and multicanonical algorithms.
平面直方图技术为模拟一级类似的相变提供了一种强大的方法，并且对于蛋白质研究可能非常有用。在这里，我们通过对肽聚集的隐溶剂全原子蒙特卡罗（MC）模拟来测试这种方法，模拟物为铜/锌超氧化物歧化酶 1 蛋白（SOD1）的 7 残基片段（GIINFEQ）[更正]。在 8 条链的模拟中，我们观察到两种不同的聚集/非聚集相。在中点温度下，这些相共存，由高度为 2.7 k（B）T 的自由能势垒隔开。我们表明，可以通过仔细实施平面直方图技术成功地研究该系统。在传统的正则模拟中，势垒穿越的频率较低，可以通过转向基于 Wang-Landau 和多正则算法的两步程序来增加。
