Stochastic modelling of protein synthesis by ribosomes
Final Report Abstract
In Project P9, we have developed detailed and quantitative stochastic models for translational elongation and tRNA recharging; for the entry of short peptide chains into the ribosomal exit tunnel; for codon optimization; for the ultra-sensitive dependence of protein synthesis on EF-Tu abundance; as well as for the competition between co- and post-translational assembly of protein subunits. Major achievements include the introduction of a new computational scheme to deduce the transition rates in vivo from their in-vitro values; the computation of the tRNA available as free ternary complexes based on the measured total tRNA concentrations; the theoretical analysis of the fluorescence data obtained by Marina Rodnina (Project P6), which revealed strongly position-dependent translation rates; a new scheme for codon optimization based on a combination of stochastic and statistical modelling; the insight that protein synthesis is ultra-sensitive to small changes in EF-Tu concentrations; and stochastic models for the co- and post-translational assembly of protein subunits.
Publications
- Deducing the kinetics of protein synthesis in vivo from the transition rates measured in vitro. PLoS Comp. Biol. 10, e1003909 (2014)
S. Rudorf, M. Thommen, M. Rodnina, and R. Lipowsky
(See online at https://doi.org/10.1371/journal.pcbi.1003909) - Protein synthesis in E. coli: Dependence of codon-specific elongation on tRNA concentration and codon usage. PLoS ONE 10, e013494 (2015)
S. Rudorf and R. Lipowsky
(See online at https://doi.org/10.1371/journal.pone.0134994) - Decomposition of time-dependent fluorescence signals reveals codon-specific kinetics of protein synthesis. Nucleic Acids Research, 46, e130 (2018)
N. Haase, W. Holtkamp, R. Lipowsky, M. Rodnina, and S. Rudorf
(See online at https://doi.org/10.1093/nar/gky740)
