Relationships between protein structure and dynamics from a database of NMR-derived backbone order parameters

The amplitude of protein backbone NH group motions on a time-scale faster t han molecular tumbling may be determined by analysis of N-15 NMR relaxation data according to the Lipari-Szabo model free formalism. An internet-acces sible database has been compiled containing 1855 order parameters from 20 i ndependent NMR relaxation studies on proteins whose three-dimensional struc tures are known. A series of statistical analyses has been performed to ide ntify relationships between the structural features and backbone dynamics o f these proteins. Comparison of average order parameters for different amin o acid types indicates that amino acids with small side-chains tend to have greater backbone flexibility than those with large side-chains. In additio n, the motions of a given NH group are also related to the sizes of the nei ghboring amino acids in the primary sequence. The secondary structural envi ronment appears to influence backbone dynamics relatively weakly, with only subtle differences between the order parameter distributions of loop struc tures and regular hydrogen bonded secondary structure elements. However, NH groups near helix termini are more mobile on average than those in the cen tral regions of helices. Tertiary structure influences are also relatively weak but in the expected direction, with more exposed residues being more f lexible on average than residues that are relatively inaccessible to solven t. (C) 2000 Academic Press.