Lee J, Scheraga H A, Rackovsky S
Department of Biomathematical Sciences, Mt. Sinai School of Medicine, New York, NY 10029, USA.
Biopolymers. 1998 Aug;46(2):103-16. doi: 10.1002/(SICI)1097-0282(199808)46:2<103::AID-BIP5>3.0.CO;2-Q.
The conformational space of the 20-residue membrane-bound portion of melittin has been investigated extensively with the conformational space annealing (CSA) method and the ECEPP/3 (Empirical Conformational Energy Program for Peptides) algorithm. Starting from random conformations, the CSA method finds that there are at least five different classes of conformations, within 4 kcal/mol, which have distinct backbone structures. We find that the lowest energy conformation of this peptide from previous investigations is not the global minimum-energy conformation (GMEC); but it belongs to the second lowest energy class of the five classes found here. In four independent runs, one conformation is found repeatedly as the lowest energy conformation of the peptide (two of the four lowest energy conformations are identical; the other two have essentially identical backbone conformations but slightly different side-chain conformations). We propose this conformation, whose energy is lower than that found previously by 1.9 kcal/mol, as the GMEC of the ECEPP/3 force field. The structure of the proposed GMEC is less helical and more compact than the previous one. It appears that the CSA method can find several classes of conformations of a 20-residue peptide starting from random conformations utilizing only its amino acid sequence information. The proposed GMEC has also been found with a modified electrostatically driven Monte Carlo method [D. R. Ripoll, A. Liwo, and H. A. Scheraga (1998) "New Developments of the Electrostatically Driven Monte Carlo Method: Test on the Membrane-Bound Portion of Melittin," Biopolymers, Vol. 46, pp. 117-126].
利用构象空间退火（CSA）方法和ECEPP/3（肽的经验构象能量程序）算法，对蜂毒肽20个残基的膜结合部分的构象空间进行了广泛研究。从随机构象开始，CSA方法发现，在4千卡/摩尔范围内，至少有五类不同的构象，它们具有不同的主链结构。我们发现，先前研究中该肽的最低能量构象不是全局最低能量构象（GMEC）；但它属于这里发现的五类中能量第二低的类别。在四次独立运行中，一种构象被反复发现为该肽的最低能量构象（四个最低能量构象中的两个相同；另外两个具有基本相同的主链构象，但侧链构象略有不同）。我们提出这种能量比先前发现的低1.9千卡/摩尔的构象作为ECEPP/3力场的GMEC。所提出的GMEC的结构比先前的结构螺旋性更低且更紧凑。似乎CSA方法仅利用其氨基酸序列信息，就能从随机构象中找到一个20个残基肽的几类构象。所提出的GMEC也通过一种改进的静电驱动蒙特卡罗方法被发现[D. R. Ripoll、A. Liwo和H. A. Scheraga（1998年）“静电驱动蒙特卡罗方法的新进展：对蜂毒肽膜结合部分的测试”，《生物聚合物》，第46卷，第117 - 126页]。
