Centre for Computational Chemistry, School of Chemistry, University of Bristol, Bristol BS8 1TS, UK.
Nat Chem. 2012 Jan 29;4(3):169-76. doi: 10.1038/nchem.1244.
The role of protein dynamics in enzyme catalysis is a matter of intense current debate. Enzyme-catalysed reactions that involve significant quantum tunnelling can give rise to experimental kinetic isotope effects with complex temperature dependences, and it has been suggested that standard statistical rate theories, such as transition-state theory, are inadequate for their explanation. Here we introduce aspects of transition-state theory relevant to the study of enzyme reactivity, taking cues from chemical kinetics and dynamics studies of small molecules in the gas phase and in solution--where breakdowns of statistical theories have received significant attention and their origins are relatively better understood. We discuss recent theoretical approaches to understanding enzyme activity and then show how experimental observations for a number of enzymes may be reproduced using a transition-state-theory framework with physically reasonable parameters. Essential to this simple model is the inclusion of multiple conformations with different reactivity.
蛋白质动力学在酶催化中的作用是当前激烈争论的问题。涉及显著量子隧穿的酶催化反应会导致具有复杂温度依赖性的实验动力学同位素效应，有人认为标准的统计速率理论（如过渡态理论）不足以解释这些效应。在这里，我们引入了与酶反应性研究相关的过渡态理论的各个方面，这些方面借鉴了气相和溶液中小分子的化学动力学和动力学研究——在这些研究中，统计理论的崩溃受到了广泛关注，其起源也相对更容易理解。我们讨论了理解酶活性的最新理论方法，然后展示了如何使用具有物理合理参数的过渡态理论框架再现许多酶的实验观察结果。这个简单模型的关键是包含具有不同反应性的多种构象。
