title: Complete protein structure determination using backbone residual dipolar couplings and sidechain rotamer prediction.
abstract: Residual dipolar couplings provide significant structural information for proteins in the solution state, which makes them attractive for the rapid determination of protein structures. While dipolar couplings contain inherent structural ambiguities, these can be reduced via an overlap similarity measure that insists that protein fragments assigned to overlapping regions of the sequence must have self-consistent structures. This allows us to determine a backbone fold (including the correct Calpha-Cbeta bond orientations) using only residual dipolar coupling data from one ordering medium. The resulting backbone structures are of sufficient quality to allow for modeling of sidechain rotamer states using a rotamer prediction algorithm and a force field employing the Surface Generalized Born continuum solvation model. We demonstrate the applicability of the method using experimental data for ubiquitin. These results illustrate the synergies that are possible between protein structural database and molecular modeling methods and NMR spectroscopy, and we expect that the further development of these methods will lead to the extraction of high resolution structural information from minimal NMR data.
authors.affiliation: Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, 610 Taylor Road, Piscataway, NJ 08854-8087, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Andrec
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Harano
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Jacobson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Friesner
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Levy
mesh_terms: D003198:Computer Simulation; D003460:Crystallization; D030562:Databases, Protein; D008958:Models, Molecular; D009010:Monte Carlo Method; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D012995:Solubility; D025801:Ubiquitin / Q000737:chemistry
chemical_list: D010446:Peptide Fragments; D025801:Ubiquitin