Codon-specific Ramachandran plots show amino acid backbone conformation depends on identity of the translated codon

Genetic code redundancies are considered inconsequential to protein structure. This study uncovers a dependence between local amino acid conformation in folded proteins and the identity of the codon from which that amino acid was translated. Synonymous codons translate into chemically identical amino acids. Once considered inconsequential to the formation of the protein product, there is evidence to suggest that codon usage affects co-translational protein folding and the final structure of the expressed protein. Here we develop a method for computing and comparing codon-specific Ramachandran plots and demonstrate that the backbone dihedral angle distributions of some synonymous codons are distinguishable with statistical significance for some secondary structures. This shows that there exists a dependence between codon identity and backbone torsion of the translated amino acid. Although these findings cannot pinpoint the causal direction of this dependence, we discuss the vast biological implications should coding be shown to directly shape protein conformation and demonstrate the usefulness of this method as a tool for probing associations between codon usage and protein structure. Finally, we urge for the inclusion of exact genetic information into structural databases.

Automated summary

This study reveals a dependence between local amino acid conformation in folded proteins and the identity of the codon from which that amino acid was translated. Synonymous codons translate into chemically identical amino acids. Codon usage affects co-translational protein folding and the final structure of the expressed protein.