Ripoll D R, Liwo A, Scheraga H A
Cornell Theory Center, Cornell University, Ithaca, NY 14853, USA.
Biopolymers. 1998 Aug;46(2):117-26. doi: 10.1002/(SICI)1097-0282(199808)46:2<117::AID-BIP6>3.0.CO;2-P.
The electrostatically driven Monte Carlo (EDMC) method has been greatly improved by adding a series of new features, including a procedure for cluster analysis of the accepted conformations. This information is used to guide the search for the global energy minimum. Alternative procedures for generating perturbed conformations to sample the conformational space were also included. These procedures enhance the efficiency of the method by generating a larger number of low-energy conformations. The improved EDMC method has been used to explore the conformational space of a 20-residue polypeptide chain whose sequence corresponds to the membrane-bound portion of melittin. The ECEPP/3 (Empirical Conformational Energy Program for Peptides) algorithm was used to describe the conformational energy of the chain. After an exhaustive search involving 14 independent runs, the lowest energy conformation (LEC) (-91.0 kcal/mol) of the entire study was encountered in four of the runs, while conformations higher in energy by no more than 1.8 kcal/mol were found in the remaining runs with the exception of one of them (run 8). The LEC is identical to the conformation found recently by J. Lee, H. A. Scheraga, and S. Rackovsky [(1988) "Conformational Analysis of the 20-Residue Membrane-Bound Portion of Melittin by Conformational Space Annealing," Biopolymers, Vol. 46, pp. 103-115] as the lowest energy conformation obtained in their study using the conformational space annealing method. These results suggest that this conformation corresponds to the global energy minimum of the ECEPP/3 potential function for this specific sequence: it also appears to be the conformation of lowest free energy.
通过添加一系列新特性，静电驱动蒙特卡罗（EDMC）方法得到了极大改进，这些特性包括对已接受构象进行聚类分析的程序。该信息用于指导寻找全局能量最小值。还纳入了生成受扰构象以对构象空间进行采样的替代程序。这些程序通过生成大量低能量构象提高了该方法的效率。改进后的EDMC方法已用于探索一条20个残基的多肽链的构象空间，其序列对应于蜂毒肽的膜结合部分。使用ECEPP/3（肽的经验构象能量程序）算法来描述该链的构象能量。在进行了14次独立运行的详尽搜索后，在其中4次运行中遇到了整个研究中能量最低的构象（LEC）（-91.0千卡/摩尔），而在其余运行中（除了其中一次运行8）发现能量比其高不超过1.8千卡/摩尔的构象。该LEC与J. Lee、H. A. Scheraga和S. Rackovsky最近发现的构象相同[（1988年）“通过构象空间退火对蜂毒肽20个残基膜结合部分的构象分析”，《生物聚合物》，第46卷，第103 - 115页]，是他们使用构象空间退火方法在研究中获得的能量最低的构象。这些结果表明，该构象对应于该特定序列的ECEPP/3势函数的全局能量最小值：它似乎也是自由能最低的构象。
