Catalysis: transition-state molecular recognition?
Catalysis: transition-state molecular recognition?
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DOI：
10.3762/bjoc.6.117
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发表时间：
2010-11-03
影响因子：
2.7
通讯作者：
Williams IH
中科院分区：
文献类型：
--
作者：
Williams IH
理解催化的基本过程的关键是过渡态(TS)：事实上，催化是一个过渡态的分子识别事件。实际目标，如设计TS类似物作为潜在药物，或设计合成催化剂(包括催化抗体)，需要事先了解TS的结构才能被模仿。讨论了计算模型研究的新旧实例，这些实例说明了这一基本概念。结果表明，反应物的结合是内在的抑制，试图设计只关注结合位置上有吸引力的相互作用的催化剂可能会失败。描述了邻苯二酚-O-甲基转移酶催化SN2甲基转移反应的自由能沿反应坐标的变化，并与水中模型反应的自由能变化进行了比较，用量子力学/分子力学混合分子动力学方法进行了计算。讨论了木聚糖酶中分子识别的情况，该酶将其糖底物稳定在(通常不利的)船形构象中，其中单原子突变显著影响激活自由能。
The key to understanding the fundamental processes of catalysis is the transition state (TS): indeed, catalysis is a transition-state molecular recognition event. Practical objectives, such as the design of TS analogues as potential drugs, or the design of synthetic catalysts (including catalytic antibodies), require prior knowledge of the TS structure to be mimicked. Examples, both old and new, of computational modelling studies are discussed, which illustrate this fundamental concept. It is shown that reactant binding is intrinsically inhibitory, and that attempts to design catalysts that focus simply upon attractive interactions in a binding site may fail. Free-energy changes along the reaction coordinate for SN2 methyl transfer catalysed by the enzyme catechol-O-methyl transferase are described and compared with those for a model reaction in water, as computed by hybrid quantum-mechanical/molecular-mechanical molecular dynamics simulations. The case is discussed of molecular recognition in a xylanase enzyme that stabilises its sugar substrate in a (normally unfavourable) boat conformation and in which a single-atom mutation affects the free-energy of activation dramatically.
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影响因子：
15
作者：
Roca, M;Martí, S;Williams, IH
通讯作者：
Williams, IH
影响因子：
4.9
作者：
Kanaan, Natalia;Pernia, J. Javier Ruiz;Williams, Ian H.
通讯作者：
Williams, Ian H.
影响因子：
15
作者：
WILKIE, J;WILLIAMS, IH
通讯作者：
WILLIAMS, IH
影响因子：
15
作者：
WILLIAMS, IH
通讯作者：
WILLIAMS, IH
影响因子：
15
作者：
GRAY, CH;COWARD, JK;SCHOWEN, RL
通讯作者：
SCHOWEN, RL