REQUIMTE-UCIBIO, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007, Porto, Portugal.
Chemphyschem. 2018 Mar 19;19(6):669-689. doi: 10.1002/cphc.201700339. Epub 2018 Jan 30.
Enzymes play a biologically essential role in performing and controlling an important share of the chemical processes occurring in life. However, despite their critical role in nature, attaining a clear understanding of the way an enzyme acts is still cumbersome. Computational enzymology is playing an increasingly important role in this field of research. It allows the elucidation of a complete and detailed mechanism of an enzymatic reaction, including the characterization of reaction intermediates and transition states from both structural and energetic points of view, which is something that no other single experiment can produce alone. In this review, we present a general computational strategy to study enzymatic mechanisms based on adiabatic mapping and free geometry optimization. These methods allow chemical reactions to be studied with high theoretical levels, and allow a more exhaustive exploration of the chemical reactional space than other available methods, albeit being limited to the extent that they explore the enzyme conformational space. Special attention is given to the choice of the theoretical levels, as well as describing the model systems that are currently used to study enzymatic reactions. With this, we aim to provide a good introduction for non-specialised users in this field of research. We also provide a selection of hand-picked examples from our own work that illustrate the power of computational enzymology to study catalytic mechanisms. Some of these studies constitute pioneering work in the field that were later validated by experimental means.
酶在执行和控制生命中发生的许多重要化学过程方面发挥着至关重要的生物学作用。然而，尽管它们在自然界中具有关键作用，但要清楚地了解酶的作用方式仍然很困难。计算酶学在这一研究领域发挥着越来越重要的作用。它允许阐明酶反应的完整和详细的机制，包括从结构和能量的角度对反应中间体和过渡态进行特征描述，这是任何其他单一实验都无法单独完成的。在这篇综述中，我们提出了一种基于绝热映射和自由几何优化的研究酶机制的一般计算策略。这些方法允许用高理论水平研究化学反应，并允许比其他可用方法更彻底地探索化学反应空间，尽管它们仅限于探索酶构象空间的程度。特别关注理论水平的选择，以及描述目前用于研究酶反应的模型系统。通过这些方法，我们旨在为该研究领域的非专业用户提供一个良好的介绍。我们还精选了一些来自我们自己工作的例子来说明计算酶学在研究催化机制方面的强大功能。其中一些研究是该领域的开创性工作，后来通过实验手段得到了验证。
