Science for Life Laboratory, Department of Chemistry - BMC, Uppsala University, BMC Box 576, S-751 23 Uppsala, Sweden.
Science for Life Laboratory, Department of Chemistry - BMC, Uppsala University, BMC Box 576, S-751 23 Uppsala, Sweden.
Curr Opin Struct Biol. 2018 Oct;52:50-57. doi: 10.1016/j.sbi.2018.08.004. Epub 2018 Sep 8.
With increasing computational power, biomolecular simulations have become an invaluable tool for understanding enzyme mechanisms and the origins of enzyme catalysis. More recently, computational studies have started to focus on understanding how enzyme activity itself evolves, both in terms of enhancing the native or new activities on existing enzyme scaffolds, or completely de novo on previously non-catalytic scaffolds. In this context, both experiment and molecular modeling provided strong evidence for an important role of conformational dynamics in the evolution of enzyme functions. This contribution will present a brief overview of the current state of the art for computationally exploring enzyme conformational dynamics in enzyme evolution, and, using several showcase studies, illustrate the ways molecular modeling can be used to shed light on how enzyme function evolves, at the most fundamental molecular level.
随着计算能力的提高，生物分子模拟已成为理解酶机制和酶催化起源的宝贵工具。最近，计算研究开始侧重于理解酶活性本身是如何进化的，无论是在增强现有酶支架上的天然或新活性，还是在以前无催化支架上完全从头开始。在这种情况下，实验和分子建模都为构象动力学在酶功能进化中的重要作用提供了有力证据。本文将简要概述计算探索酶进化中酶构象动力学的最新进展，并通过几个展示性研究来说明分子建模如何用于阐明酶功能在最基本的分子水平上是如何进化的。
