title: Torsion-angle molecular dynamics as a new efficient tool for NMR structure calculation.
abstract: Molecular dynamics in torsion-angle space was applied to nuclear magnetic resonance structure calculation using nuclear Overhauser effect-derived distances and J-coupling-constant-derived dihedral angle restraints. Compared to two other commonly used algorithms, molecular dynamics in Cartesian space and metric-matrix geometry combined with Cartesian molecular dynamics, the method shows increased computational efficiency and success rate for large proteins, and it shows a dramatically increased radius of convergence for DNA. The torsion-angle molecular dynamics algorithm starts from an extended strand conformation and proceeds in four stages: high-temperature torsion-angle molecular dynamics, slow-cooling torsion-angle molecular dynamics, Cartesian molecular dynamics, and minimization. Tests were carried out using experimental NMR data for protein G, interleukin-8, villin 14T, and a 12 base-pair duplex of DNA, and simulated NMR data for bovine pancreatic trypsin inhibitor. For villin 14T , a monomer consisting of 126 residues, structure determination by torsion-angle molecular dynamics has a success rate of 85%, a more than twofold improvement over other methods. In the case of the 12 base-pair DNA duplex, torsion-angle molecular dynamics had a success rate of 52% while Cartesian molecular dynamics and metric-matrix distance geometry always failed.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biophysics, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: E G
authors.initials: EG
authors.lastname: Stein
authors.forename: L M
authors.initials: LM
authors.lastname: Rice
authors.forename: A T
authors.initials: AT
authors.lastname: Brünger
mesh_terms: D000465:Algorithms; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry; D002417:Cattle; D004247:DNA / Q000737:chemistry; D004735:Energy Transfer; D016209:Interleukin-8 / Q000737:chemistry; D008840:Microfilament Proteins / Q000737:chemistry; D009419:Nerve Tissue Proteins / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D015203:Reproducibility of Results; D014361:Trypsin Inhibitors / Q000737:chemistry
chemical_list: D002352:Carrier Proteins; C029152:G-substrate; D016209:Interleukin-8; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D014361:Trypsin Inhibitors; C026615:villin; D004247:DNA