Centre for Computational Chemistry, School of Chemistry, University of Bristol, Bristol, UK.
Interdiscip Sci. 2010 Mar;2(1):78-97. doi: 10.1007/s12539-010-0093-y. Epub 2010 Jan 28.
Transfer of hydrogen as a proton, hydride or hydrogen atom is an important step in many enzymic reactions. Experiments show kinetic isotope effects (KIEs) for some enzyme-catalysed hydrogen transfer reactions that deviate significantly from the limits imposed by considering the differences in mass of the isotopes alone (i.e. the semiclassical limit). These KIEs can be explained if the transfer of the hydrogen species occurs via a quantum mechanical tunnelling mechanism. The unusual temperature dependence of some KIEs has led to suggestions that enzymes have evolved to promote tunnelling through dynamics - a highly controversial hypothesis. Molecular simulations have a vital role in resolving these questions, providing a level of detail of analysis not possible through experiments alone. Here, we review computational molecular modelling studies of quantum tunnelling in enzymes, in particular focusing on the enzymes soybean lipoxygenase-1 (SLO-1), dihydrofolate reductase (DHFR), methylamine dehydrogenase (MADH) and aromatic amine dehydrogenase (AADH) to illustrate the current controversy regarding the importance of quantum effects in enzyme catalysis.
氢作为质子、氢化物或氢原子的转移是许多酶促反应中的重要步骤。实验表明，一些酶催化的氢转移反应的动力学同位素效应（KIE）与仅考虑同位素质量差异所施加的限制明显偏离（即半经典极限）。如果氢物种的转移是通过量子力学隧穿机制发生的，则可以解释这些 KIE。一些 KIE 的异常温度依赖性导致了这样的建议，即酶已经进化为通过动力学促进隧穿——这是一个极具争议的假设。分子模拟在解决这些问题方面发挥着至关重要的作用，提供了仅凭实验无法实现的分析细节。在这里，我们回顾了关于酶中量子隧穿的计算分子建模研究，特别是重点关注大豆脂氧合酶-1（SLO-1）、二氢叶酸还原酶（DHFR）、甲胺脱氢酶（MADH）和芳香胺脱氢酶（AADH），以说明当前关于量子效应在酶催化中的重要性的争议。
