title: Computer-aided conformational analysis based on NOESY signal intensities.
abstract: The basis for the development of a suite of programs that allow the user to determine motional features (the correlation time and the significance of segmental motion) and the optimum conditions for future experiments from a NOESY signal matrix is presented. This automated evaluation of NOESY data serves as the initial step of an iterative conformational analysis which uses the molecular model manipulation capabilities of modern graphics workstations. Incorporated in these programs is NOESYSIM, a calculation subroutine which uses a set of molecular coordinates (and a correlation time estimate) together with user entered experimental parameters (acquisition time, sweep width, mixing time and cycle repetition time) to generate an accurately calculated NOESY signal matrix reflecting those conditions and the specified conformational model. Conformational refinement then consists of iterative comparisons of the experimental signal matrix with a series (or systematically sampled set) of model coordinates corresponding to a dynamics' course, driven-minimization or torsional grid search. These procedures and developments are illustrated with examples including: solution conformations of prostanoids; studies of the folding preferences and media-dependent changes in conformation for peptide hormones; and the structure elucidation of a novel undecapeptide macrolide antibiotic (lysobactin). For larger molecules, even constrained grid searches have too high a dimensionality and one must resort to distance-constraint based minimizations. A novel procedure for deriving more accurate distance constraints (corrected for secondary NOEs) is detailed and a new strategy for conformation elucidation, based on this procedure, is outlined.
authors.affiliation: Department of Chemistry, University of Washington, Seattle 98195.
authors.forename: N H
authors.initials: NH
authors.lastname: Andersen
authors.forename: X N
authors.initials: XN
authors.lastname: Lai
authors.forename: P K
authors.initials: PK
authors.lastname: Hammen
authors.forename: T M
authors.initials: TM
authors.lastname: Marschner
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry; D003198:Computer Simulation; D047630:Depsipeptides; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008433:Mathematics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D012984:Software
chemical_list: D000900:Anti-Bacterial Agents; D047630:Depsipeptides; D009842:Oligopeptides; D010455:Peptides; C056790:katanosin B