亮氨酸脑啡肽构象的分子动力学方法研究(英文)

Conformational Analysis of Leu-enkephalin by Molecular Dynamics Method

采用淬火和模拟退火两种分子动力学的方法对亮氨酸脑啡肽进行了构象搜索，发现了多个Gly－Pheβ－Ⅱ’转角的低能构象．计算结果表明，高温淬火和模拟退火两者结合起来可以有效地寻找低能构象．

Leu-enkephalin (Try-Gly-Gly-Phe-Leu) is an endogenous opioid pentapeptide with biological effects similar to morphine. Researches on its structure and conformational analysis have been reported in past few years([2-5]), however, most of the researches on leu-eukephalin have concerned only with the crystal structure. Unlike another enkephalin - met-enkephalin, leu-enkephalin, hasn't been fully studied by lots of conformational search methods. The global energy minimum conformation may not be the bioactive form that binds with the opioid receptors, so, to search set of low energy conformations with energy close to global minimum are nesseary. In this paper, an extensive exploration of the conformation space of Leu-enkephalin have been carried out. Two kinds of MD (quenching and annealing) methods were used for this purpose. The lowest energy structure found with a distance dependent dielectric constant was Gly - Phe beta II-type turn, Multiple fit have been performed with morphine for all the low energy conformational domains.