CATALYTIC STRATEGIES OF CHOLINESTERASES & TRYPSIN: MOLECULAR DYNAMICS STUDIES

胆碱酯酶的催化策略

• 批准号: 6282513
• 负责人: ILDIKO M KOVACH
• 金额: $ 1.19万
• 依托单位: MELLON PITTS CORPORATION (MPC CORP)
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6282513
• 关键词: biological products; biomedical resource; computers

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.

这是解决基本问题的提案 小分子乙酰胆碱酯酶（AChE）的催化和抑制 使用 CHARMM 的分子动力学模拟。 两项当前任务 是最近提出的门控机制的模拟 溶剂化物活性位点空腔中的胆碱和乙酸根离子 AChE 相互作用的蛋白质和动力学计算 -索曼非对映异构体。 为了评估 AChE 的渗透性 单体到小型 ios，至少 150 ps 的完整模拟应该是 执行。 另一个问题是催化组氨酸的迁移率 以及其在天然 AChE 中最小构象的位置和 分别与胰蛋白酶相比，磷酸化 AChE。 其他动态 与胰蛋白酶相比，活性位点的成分也会 被研究。