物理化学学报 >> 2017, Vol. 33 >> Issue (4): 691-708.doi: 10.3866/PKU.WHXB201612191

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酶催化过程的全程模拟

赵媛1,曹泽星2,*()   

  1. 1 河南大学天然药物与免疫工程重点实验室,河南开封475004
    2 厦门大学化学化工学院,福建省理论与计算化学重点实验室,福建厦门361005
  • 收稿日期:2016-10-28 发布日期:2017-03-23
  • 通讯作者: 曹泽星 E-mail:zxcao@xmu.edu.cn
  • 作者简介:赵媛,1987年生。2015年于厦门大学获取理学博士学位,现为河南大学天然药物与免疫工程重点实验室讲师。现主要从事生物体系多尺度计算模拟及计算机辅助药物设计相关领域的研究|曹泽星,1962年生。现为厦门大学化学化工学院教授,博士生导师。研究兴趣包括:激发态与光化学、无机与金属有机化学反应机理、复杂体系与酶催化过程的多尺度模拟、低维纳米材料的计算设计与模拟
  • 基金资助:
    国家自然科学基金(21133007);国家自然科学基金(21373164);国家自然科学基金(21172053)

Global Simulations of Enzymatic Catalysis

Yuan ZHAO1,Ze-Xing CAO2,*()   

  1. 1 Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, Henan Province, P. R. China
    2 Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 360015, Fujian Province, P. R. China
  • Received:2016-10-28 Published:2017-03-23
  • Contact: Ze-Xing CAO E-mail:zxcao@xmu.edu.cn
  • Supported by:
    The project was supported by the National Natural Science Foundation of China(21133007);The project was supported by the National Natural Science Foundation of China(21373164);The project was supported by the National Natural Science Foundation of China(21172053)

摘要:

酶催化包括底物到活性区的输运、选择催化化学反应及产物释放等复杂过程,由于复杂的蛋白质环境效应,任一化学和非化学过程都有可能是决定酶活性的关键步骤。为了全面认识酶催化活性,我们对几类酶催化过程进行了广泛的组合量子/分子力学(QM/MM)和经典分子力学(MM)动力学模拟(MD)研究,详细地讨论了整个酶催化过程的分子机制、关键残基的作用和蛋白质环境效应,丰富了对酶催化活性的认识。随着多尺度模型和计算模拟方法的进一步完善与发展,有望实现超大复杂生物酶催化过程的全程模拟研究,为酶工程领域的相关研究提供支持。

关键词: 酶催化, 底物输运, 自由能计算, QM/MM MD模拟, 随机加速动力学模拟

Abstract:

Enzymatic catalytic processes generally involve substrate delivery, selective catalytic reaction, and product release. Owing to the complex protein environment effect, any nonchemical or chemical step may determine the enzyme activity. Herein, to comprehensively understand enzymatic activity, extensive combined quantum mechanics/molecular mechanics (QM/MM) and molecular mechanics (MM) molecular dynamics (MD) simulations were carried out on several kinds of enzymes. Possible reaction mechanisms, roles of the conserved residues, and effects of the protein environment on the whole enzymatic process are discussed in detail, which will enrich the knowledge of reactivity in proteins. With the improvement and development of multiscale models and computational methods, it is expected that global simulations of extremely large and complicated enzymes will enable and lend support to enzyme engineering.

Key words: Enzymatic catalysis, Substrate delivery, Free energy calculations, QM/MM MD simulation, Random acceleration molecular dynamics (DAMD) simulation

MSC2000: 

  • O641