Ribosome Kinetics and Aa-tRNA Competition Determine Rate and Fidelity of Peptide Synthesis

It is well established that translation, the process by which the ribosome synthesizes proteins, proceeds at a varying rate, but several theories have been proposed for this variation. We have hypothesized that the cognate aminoacyl tRNA (aa-tRNA) faces competition for binding at the ribosome from near- and non-cognate aa-tRNAs, causing the observed delays and errors in peptide synthesis. We have calculated the competition levels, translation times, and error frequencies for all 64 RNA codons. The model sheds light on the arrangement of fast- and slow-translating regions in a particular gene and the kinetics of programmed frameshifts.