Editing Codon usage bias (section)

=== Effect on protein folding ===
[[Protein folding]] ''in vivo'' is [[Vectorial space|vectorial]], such that the [[N-terminus]] of a protein exits the translating ribosome and becomes solvent-exposed before its more [[C-terminal]] regions. As a result, co-translational protein folding introduces several spatial and temporal constraints on the nascent polypeptide chain in its folding trajectory. Because mRNA translation rates are coupled to protein folding, and codon adaptation is linked to translation elongation, it has been hypothesized that manipulation at the sequence level may be an effective strategy to regulate or improve protein folding. Several studies have shown that pausing of translation as a result of local mRNA structure occurs for certain proteins, which may be necessary for proper folding. Furthermore, [[synonymous mutations]] have been shown to have significant consequences in the folding process of the nascent protein and can even change substrate specificity of enzymes. These studies suggest that codon usage influences the speed at which [[peptide|polypeptides]] emerge vectorially from the ribosome, which may further impact protein folding pathways throughout the available structural space.<ref name = "doi1" />