Theoretical Study on Two-Step Mechanisms of Peptide Release in the Ribosome

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• 作者：Carles Acosta-Silva ; Joan Bertran ; Vicen莽 Branchadell ; Antoni Oliva
• 刊名：Journal of Physical Chemistry B
• 出版年：2014
• 出版时间：May 29, 2014
• 年：2014
• 卷：118
• 期：21
• 页码：5717-5729
• 全文大小：551K
• 年卷期：v.118,no.21(May 29, 2014)
• ISSN：1520-5207

文摘

A quantum mechanical study of different two-step mechanisms of peptide release in the ribosome has been carried out using the M06-2X density functional. Reoptimization with MP2 has also been carried out for the stationary points of some selected mechanisms. The uncatalyzed processes in solution have been treated with the SMD solvation model. From the results obtained in this paper for the peptide release process we can conclude that the energy barriers for the two-step mechanisms are lower than the ones for the concerted process, that the 2鈥睴H plays also an important role in the catalytic process and that the side chain does not only accommodate a nucleophilic water molecule in the PTC, but it also contributes to activate this molecule through electron transfer to the water oxygen. We have also found that the second step is the rate-determining one, and that the two most favorable mechanisms, in which a water or a formamide molecule is added, follow a quite different strategy to catalyze the reaction. The main conclusion of our work is that the two-step mechanisms cannot be disregarded, since they can contribute to clarify the complex and yet unsolved problem of the mechanism of the peptide release process.