Åqvist Johan, Brandsdal Bjørn O
Department of Cell & Molecular Biology, Uppsala University, Biomedical Center, SE-751 24 Uppsala, Sweden.
Department of Chemistry, University of Tromsø - The Arctic University of Norway, N9037 Tromsø, Norway.
J Chem Theory Comput. 2025 Feb 11;21(3):1017-1028. doi: 10.1021/acs.jctc.4c01733. Epub 2025 Jan 30.
In this review we discuss the development of methodology for calculating the temperature dependence and thermodynamic activation parameters for chemical reactions in solution and in enzymes, from computer simulations. We outline how this is done by combining the empirical valence bond method with molecular dynamics free energy simulations. In favorable cases it turns out that such simulations can even capture temperature optima for the catalytic rate. The approach turns out be very useful both for addressing questions regarding the roles of enthalpic and entropic effects in specific enzymes and also for attacking evolutionary problems regarding enzyme adaptation to different temperature regimes. In the latter case, we focus on cold-adaptation of enzymes from psychrophilic species and show how computer simulations have revealed the basic mechanisms behind such adaptation. Understanding these mechanisms also opens up the possibility of designing the temperature dependence, and we highlight a recent example of this.
在本综述中，我们讨论了通过计算机模拟计算溶液中和酶中化学反应的温度依赖性及热力学活化参数的方法的发展。我们概述了如何将经验价键方法与分子动力学自由能模拟相结合来实现这一点。在有利的情况下，结果表明此类模拟甚至能够捕捉催化速率的温度最优值。事实证明，该方法对于解决有关特定酶中焓效应和熵效应作用的问题，以及解决有关酶适应不同温度范围的进化问题都非常有用。在后一种情况下，我们聚焦于嗜冷物种中酶的冷适应性，并展示计算机模拟如何揭示了这种适应性背后的基本机制。理解这些机制也为设计温度依赖性开辟了可能性，我们着重介绍了这方面的一个最新实例。
