LAUSR

Coupling of side chain dynamics over long distances is an important component of allostery. Methionine side chains show the largest intrinsic flexibility among methyl‐containing residues but the actual degree of conformational averaging depends on the proximity and mobility of neighboring residues. The 13C NMR chemical shifts of the methyl groups of methionine residues located at long distances in the same protein show a similar scaling with respect to the values predicted from the static X‐ray structure by quantum methods. This results in a good linear correlation between calculated and observed chemical shifts. The slope is protein dependent and ranges from zero for the highly flexible calmodulin to 0.7 for the much more rigid calcineurin catalytic domain. The linear correlation is indicative of a similar level of side‐chain conformational averaging over long distances, and the slope of the correlation line can be interpreted as an order parameter of the global side‐chain flexibility.