Molecular dynamics (MD) simulations have been performed to study the dynamic behavior of noncovalent enzyme carbocation complexes involved in the cyclization of geranylgeranyl diphosphate to taxadiene catalyzed by taxadiene synthase (TXS). Taxadiene and the observed four side products originate from the deprotonation of carbocation intermediates. The MD simulations of the TXS carbocation complexes provide insights into potential deprotonation mechanisms of such carbocations. The MD results do not support a previous hypothesis that carbocation tumbling is a key factor in the deprotonation of the carbocations by pyrophosphate. Instead water bridges are identified which may allow the formation of side products via multiple proton transfer reactions. A novel reaction path for taxadiene formation is proposed on the basis of the simulations. © 2018 Wiley Periodicals, Inc.

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紫杉二烯合酶催化的分子动力学研究

已进行分子动力学 (MD) 模拟以研究非共价酶碳阳离子复合物的动态行为，该复合物参与紫杉二烯合酶 (TXS) 催化的香叶基香叶基二磷酸环化为紫杉二烯。紫杉二烯和观察到的四种副产物源自碳正离子中间体的去质子化。TXS 碳正离子配合物的 MD 模拟提供了对此类碳正离子潜在去质子化机制的见解。MD 结果不支持先前的假设，即碳正离子翻滚是焦磷酸盐对碳正离子去质子化的关键因素。相反，确定了水桥，这可能允许通过多个质子转移反应形成副产物。在模拟的基础上提出了一种新的紫杉二烯形成反应路径。