The ribosome catalyses peptide bond formation by providing high ionic strength

Johannes Kästner (1) , Paul Sherwood (2)

1 Institute for theoretical Chemistry
2 Computational Science and Engineering Department

We performed QM/MM simulations based on density functional theory (DFT) and the density-functional tight binding method (DFTB) to investigate the reaction mechanism of the peptide-bond formation in the ribosome in atomistic detail. We found the key role of the ribosome in the increased availability of mobile cations, the counter-ions to the negatively-charged RNA. We found a hydrogen transfer to occur in two mechanisms: a direct transfer, and a proton shuttle mechanism via a ribose-2'-OH group. It was found to be vital to calculate the energy barrier in numerous snapshots taken from molecular dynamics simulations and average them. Advantages and disadvantages of an exponential average compared to a direct average between the snapshots are discussed. An energy decomposition of the QM/MM results showes that the catalytic function is caused by the electrostatic influence of the environment rather than by mere positioning of the reactants. The free energy of activation for the direct proton transfer mechanism was calculated by umbrella sampling. It confirmed a moderate entropic contribution to the activation free energy found in experiment. Overall, this study increases our understanding of the catalytic mechanism of the ribosome and probably also other ribozymes.

Mots clés: Physical Sciences

Johannes Kästner, Paul Sherwood. The ribosome catalyses peptide bond formation by providing high ionic strength. Molecular Physics, 2010, 108 (03-04), pp.293-306. ⟨10.1080/00268970903446764⟩. ⟨hal-00580694⟩