REPACKING PROTEIN CORES WITH BACKBONE FREEDOM - STRUCTURE PREDICTION FOR COILED COILS

Progress in homology modeling and protein design has generated considerable interest in methods for predicting side-chain packing in the hydrophobic cores of proteins. Present techniques are not practically useful, however, because they are unable to model protein main-chain flexibility, Parameterization of backbone motions may represent a general and efficient method to incorporate backbone relaxation into such fixed main-chain models, To test this notion, we introduce a method for treating explicitly the backbone motions of cr-helical bundles based on an algebraic parameterization proposed by Francis Crick in 1953 [Crick, P. H. C. (1953) Acta Crystallogr, 6, 685-689], Given only the core amino acid sequence, a simple calculation can rapidly reproduce the crystallographic main-chain and core side-chain structures of three coiled coils (one dimer, one trimer, and one tetramer) to within 0.6-Angstrom root-mean-square deviations. The speed of the predictive method [approximate to 3 min per rotamer choice on a Silicon Graphics (Mountain View, CA) 4D/35 computer] permits it to be used as a design tool.