STANDARD-GEOMETRY CHAINS FITTED TO X-RAY DERIVED STRUCTURES - VALIDATION OF THE RIGID-GEOMETRY APPROXIMATION .1. CHAIN CLOSURE THROUGH A LIMITED SEARCH OF LOOP CONFORMATIONS

The GoBAR-Scheraga algorithm to produce rigid-geometry chain closures for polypeptide chains (N. GoBAR and H.A. Scheraga, Macromolecules, 3, 178, 1970) has been updated to allow each residue in the chain to adopt different bond lengths or bond angles. A treatment of five-residue local chain deformations is presented in detail. For chain sections shorter than five residues in length, it is shown that satisfactory closures may be obtained by direct fitting, indicating that the rigid-geometry approximation is adequate to model even short sections of chains having perturbed local geometry. The new implementation of the algorithm has been applied to several problems in protein structure determination and molecular modeling. The first of these is the problem of finding standard-geometry closures for short regions of chains having irregular geometry. It is shown that standard-geometry closures which superimpose well upon the coordinates of the irregular structures may be obtained routinely for chain sections that are five amino acid residues or more in length. Another application of the algorithm is to generate a large number of closures for a short segment of a protein chain, as a method to search the conformational space of this segment. The latter application should prove useful in studies in which the conformation of some region of a given protein has not been determined experimentally. Such applications include the modeling of proteins which have a sequence homology to a crystallized protein, and modeling regions of crystallized proteins which are not well-defined in electron density maps.