CATALYTIC STRATEGIES OF CHOLINESTERASES & TRYPSIN: MOLECULAR DYNAMICS STUDIES

这是一项解决以下基本问题的建议 小分子对乙酰胆碱酯酶(AChE)的催化和抑制 使用CHARMM的分子动力学模拟。两项当务之急 是对最近提出的门控机制的模拟 胆碱和醋酸根离子在溶剂化的活性部位空腔中 乙酰胆碱酯酶相互作用的蛋白质和动力学计算 -梭曼非对映异构体。为了评估AChE的通透性 从单体到小型IO，至少要有150ps的全模拟 被执行。另一个问题是催化组氨酸的流动性。 以及其最小构象在天然AChE和AChE中的位置 磷酸化的AChE分别与胰酶进行比较。他者的动态 活性部位的成分与胰酶的成分相比也将 被研究。

This is a proposal for addressing basic questions of acetylcholinesterase(AChE) catalysis and inhibition by small molecules using molecular dynamics simulations by CHARMM. Two immediate tasks are the simulation of the recently proposed gating mechanism with choline and acetate ion in the active site cavity of the solvated protein and dynamics calculations of the interactions in the AChE -soman diastereomers. In order to assess the permeability of the AChE monomer to small ios, an at least 150 ps full simulation should be carried out. Another question is the mobility of the catalytic His and the location of its minimum conformations in native AChE and phosphonylated AChE each compared to trypsin. The dynamics of other components of the active site as compared to that of trypsin will also be studied.