Gherib Rami, Dokainish Hisham M, Gauld James W
Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON N9B 3P4, Canada.
Int J Mol Sci. 2013 Dec 31;15(1):401-22. doi: 10.3390/ijms15010401.
Elucidating the origin of enzymatic catalysis stands as one the great challenges of contemporary biochemistry and biophysics. The recent emergence of computational enzymology has enhanced our atomistic-level description of biocatalysis as well the kinetic and thermodynamic properties of their mechanisms. There exists a diversity of computational methods allowing the investigation of specific enzymatic properties. Small or large density functional theory models allow the comparison of a plethora of mechanistic reactive species and divergent catalytic pathways. Molecular docking can model different substrate conformations embedded within enzyme active sites and determine those with optimal binding affinities. Molecular dynamics simulations provide insights into the dynamics and roles of active site components as well as the interactions between substrate and enzymes. Hybrid quantum mechanical/molecular mechanical (QM/MM) can model reactions in active sites while considering steric and electrostatic contributions provided by the surrounding environment. Using previous studies done within our group, on OvoA, EgtB, ThrRS, LuxS and MsrA enzymatic systems, we will review how these methods can be used either independently or cooperatively to get insights into enzymatic catalysis.
阐明酶催化的起源是当代生物化学和生物物理学面临的重大挑战之一。计算酶学的最新出现增强了我们对生物催化的原子水平描述以及其机制的动力学和热力学性质。存在多种计算方法可用于研究特定的酶性质。小型或大型密度泛函理论模型允许比较大量的机制反应物种和不同的催化途径。分子对接可以模拟嵌入酶活性位点内的不同底物构象，并确定具有最佳结合亲和力的构象。分子动力学模拟提供了对活性位点成分的动力学和作用以及底物与酶之间相互作用的见解。混合量子力学/分子力学（QM/MM）可以在考虑周围环境提供的空间和静电贡献的同时对活性位点中的反应进行建模。利用我们小组之前对OvoA、EgtB、ThrRS、LuxS和MsrA酶系统所做的研究，我们将回顾如何单独或协同使用这些方法来深入了解酶催化。
