DISTRIBUTED TORSION ANGLE GRID SEARCH IN HIGH DIMENSIONS - A SYSTEMATIC-APPROACH TO NMR STRUCTURE DETERMINATION

Two complementary approaches for systematic search in torsion angle sp ace are described for the generation of all conformations of polypepti des which satisfy experimental NMR restraints, hard-sphere van der Waa ls radii, and rigid covalent geometry. The first procedure is based on a recursive, tree search algorithm for the examination of linear chai ns of torsion angles, and uses a novel treatment to propagate the sear ch results to neighboring regions so that the structural consequences of the restraints are fully realized. The second procedure is based on a binary combination of torsion vector spaces for connected submolecu les, and produces intermediate results in Cartesian space for a more r obust restraint analysis. Restraints for NMR applications include boun ds on torsion angles and internuclear distances, including relational and degenerate restraints involving equivalent and nonstereoassigned p rotons. To illustrate these methods, conformation search results are g iven for the tetrapeptide APGA restrained to an idealized beta-turn co nformation, an alanine octapeptide restrained to a right-handed helica l conformation, and the structured region of the peptide SYPFDV.