title: Ab initio QM/MM free energy simulations of peptide bond formation in the ribosome support an eight-membered ring reaction mechanism.
abstract: 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.
authors.affiliation: State Key Laboratory of Precision Spectroscopy, Institute of Theoretical and Computational Science, Department of Physics, East China Normal University, Shanghai 200062, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: John Z H
authors.initials: JZ
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Xiang
mesh_terms: D055162:Biocatalysis; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D010458:Peptidyl Transferases / Q000737:chemistry* / Q000378:metabolism*; D014176:Protein Biosynthesis; D011487:Protein Conformation; D011789:Quantum Theory; D012270:Ribosomes / Q000201:enzymology / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D010455:Peptides; D010458:Peptidyl Transferases