锌酶的计算模拟
Computational Simulations of Zinc Enzyme
Abstract
锌酶扮演了许多重要的生物角色,它们在功能和结构组织上都非常依赖锌结合位点。通常,锌酶体系的锌配位结构十分复杂,可靠的计算模拟需要采用精确且高效的理论方法。我们应用量子力学/分子力学(QM/MM)组合方法,研究了4个Zn酶体系:磷酸葡萄糖异构酶(PGI)、鼠李糖异构酶(L-RhI)、组蛋白去乙酰化酶HDAC8以及嗜热菌蛋白酶(TLN),预测了酶反应机理,探讨了酶催化过程中的蛋白质动力学效应,揭示了保守残基调控催化活性的结构本质。考虑到锌酶中Zn的配位结构具有多变的配位模式、且目前的分子力场不能合理描述这一配位特征,基于QM/MM分子动力学模拟以及力匹配(ForceMatching)方法,我们发展... Zinc enzymes play a variety of essential biological roles. Their functions and/or structural organizations are critically dependent on the zinc binding site. However, the zinc coordination shell is so complicated that an accurate and powerful theoretical simulation protocol is highly required in calculation. Herein, we employed QM/MM MD simulations to explore four kinds of zinc enzymes, including ...