CATALYTIC STRATEGIES OF CHOLINESTERASES & TRYPSIN: MOLECULAR DYNAMICS STUDIES

这是一项解决以下基本问题的建议： 乙酰胆碱酯酶（AChE）的小分子催化和抑制 使用CHARMM的分子动力学模拟。 两项紧迫任务 是最近提出的门控机制的模拟， 胆碱和乙酸根离子在活性中心空腔的溶剂化 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。 为了评估乙酰胆碱酯酶的渗透性， 单体到小ios，至少150 ps的完整模拟应该是 贯彻 另一个问题是催化性的希 及其在天然乙酰胆碱酯酶中最小构象的位置， 与胰蛋白酶相比， 其他动态 与胰蛋白酶相比，活性部位的组分也 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.