Correlation between 2H NMR side-chain order parameters and sequence conservation in globular proteins.

Side-chain 2H NMR relaxation data have been collected for the SH3 domain from the Fyn tyrosine kinase and analyzed with respect to sequence preference and per-residue solvent accessibility. Residues that are highly preferred at a given position show a tendency to be less mobile than average with a coefficient of correlation that is greater than that obtained when side-chain flexibility and solvent accessibility are compared. The same trend is observed for five of six additional proteins considered. This provides evidence for the existence of conserved structural features other than hydrophobic burial that govern side-chain motions. Through examination of an SH3 domain structural alignment, we identify side-chain hydrogen bonding of threonine residues and a specific secondary structural element as potential determinants of protein internal dynamics.