title: Filtering and selection of structural models: combining docking and NMR.
abstract: It is generally accepted that protein structures are more conserved than protein sequences, and 3D structure determination by computer simulations have become an important necessity in the postgenomic area. Despite major successes no robust, fast, and automated ab initio prediction algorithms for deriving accurate folds of single polypeptide chains or structures of intermolecular complexes exist at present. Here we present a methodology that uses selection and filtering of structural models generated by docking of known substructures such as individual proteins or domains through easily obtainable experimental NMR constraints. In particular, residual dipolar couplings and chemical shift mapping are used. Heuristic inclusion of chemical or biochemical knowledge about point-to-point interactions is combined in our selection strategy with the NMR data and commonly used contact potentials. We demonstrate the approach for the determination of protein-protein complexes using the EIN/HPr complex as an example and for establishing the domain-domain orientation in a chimeric protein, the recently determined hybrid human-Escherichia. coli thioredoxin.
authors.affiliation: Laboratory of Chemical Physics, Building 5, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Anatoliy
authors.initials: A
authors.lastname: Dobrodumov
authors.forename: Angela M
authors.initials: AM
authors.lastname: Gronenborn
mesh_terms: D000465:Algorithms; D001426:Bacterial Proteins; D018360:Crystallography, X-Ray; D029968:Escherichia coli Proteins / Q000737:chemistry; D006801:Humans; D046911:Macromolecular Substances; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000737:chemistry; D017852:Phosphotransferases (Nitrogenous Group Acceptor) / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D013879:Thioredoxins / Q000737:chemistry / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D046911:Macromolecular Substances; D011993:Recombinant Fusion Proteins; D013879:Thioredoxins; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System; C030182:phosphocarrier protein HPr; D017852:Phosphotransferases (Nitrogenous Group Acceptor); C022360:phosphoenolpyruvate-protein phosphotransferase