A close-up view of codon selection in eukaryotic initiation.

When given an option to choose among a set of alternatives and only one selection is right, one might stop and reflect over which one is best. However, the ribosome has no time to stop and make such reflections, proteins need to be produced and very fast. Eukaryotic translation initiation is an example of such a conundrum. Here, scanning for the correct codon match must be fast, efficient and accurate. We highlight our recent computational findings, which show how the initiation machinery manages to recognize one specific codon among many possible challengers, by fine-tuning the energetic landscape of base-pairing with the aid of the initiation factors eIF1 and eIF1A. Using a recent 3-dimensional structure of the eukaryotic initiation complex we have performed simulations of codon recognition in atomic detail. These calculations provide an in-depth energetic and structural view of how discrimination against near-cognate codons is achieved by the initiation complex.