State Key Laboratory of Precision Spectroscopy, Institute of Theoretical and Computational Science, Department of Physics, East China Normal University, Shanghai 200062, China.
J Am Chem Soc. 2012 Oct 3;134(39):16424-9. doi: 10.1021/ja3076605. Epub 2012 Sep 20.
Ab initio QM/MM free-energy simulations were carried out to study the peptide bond formation reaction in the peptidyl transferase center of the ribosome. The QM part of the reaction was treated by density functional theory at the B3LYP/6-31G* level, while the MM part including the solvent and RNA environment was described by molecular force field. The calculated free-energy surfaces for the two popular reaction mechanisms, the six- and eight-membered ring reactions, exhibited large energetic differences which favor the eight-membered reaction mechanism. The simulated quasi-transition state structures clearly indicated a "late" feature consistent with previous theoretical studies. Also the important functional role played by water molecules in the active site of the ribosome and its implication in ribozymic catalysis was discussed in detail.
采用从头算量子力学/分子力学（QM/MM）自由能模拟方法研究核糖体肽酰转移酶中心的肽键形成反应。在 B3LYP/6-31G*水平上，用密度泛函理论处理反应的 QM 部分，而包括溶剂和 RNA 环境的 MM 部分则用分子力场来描述。对两种流行的反应机制，即六元环和八元环反应，计算得到的自由能表面显示出很大的能量差异，有利于八元环反应机制。模拟的拟过渡态结构清楚地表明了与以前理论研究一致的“晚期”特征。还详细讨论了水分子在核糖体活性部位所起的重要功能作用及其对核酶催化的影响。
