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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.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most abundant chronic liver disorder, because racial and ethnic differences may influence prevalence and severity of NAFLD. Objectives: This metabolomic study was conducted to identify the metabolic biomarkers and determine the mechanism of progress of NAFLD in Iranian patients. Methods: Serum samples were collected from 75 participants (37 healthy controls and 38 patients with NAFLD) after an overnight fast. The metabolome of all samples were determined by nuclear magnetic resonance (NMR) and were compared by multivariate statistical analysis. Results: Totally, 19 metabolomic biomarkers were identified by NMR. Compared to healthy controls, NAFLD patients had increased serum concentrations of glycochenodeoxycholic acid, taurocholic acid, glycocholic acid, deoxycholic acid, valine, isoleucine, succinic acid, isocitric acid, 2-ketoglutaric acid, trimethylamine, proline, hydroxyproline and tyrosine, while the concentrations of butyric acid, propionic acid, isovaleric acid, glutamine, glycine, and serine decreased. Conclusions: A robust set of biomarkers for diagnosis of NAFLD was established. Serum metabolomics biomarkers revealed changes in some amino acids and their derivatives, bile acids, short chain fatty acids, and tricarboxylic acid cycle intermediates in subjects with NAFLD compared to healthy controls. These markers could be used as indicators regarding the efficacy of therapeutic interventions.