Ab initio QM/MM free energy simulations of peptide bond formation in the ribosome support an eight-membered ring reaction mechanism

Jun Xu, John Z.H. Zhang, Yun Xiang

Research output: Contribution to journalArticle


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.

Original languageEnglish (US)
Pages (from-to)16424-16429
Number of pages6
JournalJournal of the American Chemical Society
Issue number39
StatePublished - Oct 3 2012


ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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