Strain in protein structures as viewed through nonrotameric side chains: I. Their position and interaction

We studied the relative spatial positioning of nonrotameric side chains wit h atypical and strained dihedral angles in well-refined protein tertiary st ructures. The analysis was confined to buried protein cores, which are less error prone to side-chain positioning. More than half of the proteins with two or more nonrotameric residues displayed clusters of two or more (and u p to five) nonrotameric residues. The clusters exhibited lower average crys tallographic temperature factors compared with isolated nonrotameric residu es. Nonrotameric clusters showed significantly tighter packing than corresp onding rotameric clusters and had distinct residue compositions that did no t correlate With amino acid characteristics such as size, hydrophobicity, t urn preference, and the like. Such nonrotameric residue biases would sugges t that spatially concentrated strain in protein folds would be minimized by lowered vibrational energy, Furthermore, nonrotameric residues avoided hel ices and strands and mostly preferred coil regions. If they were in the hel ical conformation, then they preferred to be within N-terminal segments. (C ) 1999 Wiley-Liss, Inc.