锌酶在人体中分布非常广泛,种类繁多,是当前最受关注的金属酶之一。由于在锌配位结构上的多样性以及zn2+饱和的d轨道带来的“光谱寂静“性,导致许多实验研究手段受限。计算模拟在锌酶的研究中发挥着越来越重要的作用,已经成为不可或缺的研究工具。现代量子化学计算模拟方法,特别是被视为研究生物大分子体系非常有效的QM/MM组合方法,目前已经被广泛应用于探讨复杂多变的锌配位结构以及锌酶催化反应机理。通过在QM/MM水平下开展的分子动力学模拟,可以揭示锌酶体系中结构与功能间的相互关系。此外,分子力场方法在锌酶研究中同样发挥了不可替代的作用,由于传统力场普遍无法正确描述锌配位结构,因此,锌酶分子力场的开发具有迫切的现实意义。本文总结了近年来锌酶计算模拟领域的最新进展,提出了锌酶计算研究中还有待解决的一些问题。Zinc enzymes play a variety of essential biological roles,and 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 review the recent studies of the selected zinc enzymes by the state-of-the-art combined quantum mechanism/molecular mechanism molecular dynamics(QM/MM MD) simulations in probing the reaction mechanism and revealing the relationship of structure and function.Meanwhile,the accuracy of all the current available pairwise force fields to describe zinc coordination structure is very poor,so the recent development of force fields for zinc enzyme is also presented.By the end of this review,some prospects and suggestions are given for further exploration of zinc enzyme.国家重点基础研究发展计划(973)项目(No.2011CB808504;2012CB214902);国家自然科学基金项目(No.2133007;20873105)资
