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
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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
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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
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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
