title: Consistent blind protein structure generation from NMR chemical shift data.
abstract: Protein NMR chemical shifts are highly sensitive to local structure. A robust protocol is described that exploits this relation for de novo protein structure generation, using as input experimental parameters the (13)C(alpha), (13)C(beta), (13)C', (15)N, (1)H(alpha) and (1)H(N) NMR chemical shifts. These shifts are generally available at the early stage of the traditional NMR structure determination process, before the collection and analysis of structural restraints. The chemical shift based structure determination protocol uses an empirically optimized procedure to select protein fragments from the Protein Data Bank, in conjunction with the standard ROSETTA Monte Carlo assembly and relaxation methods. Evaluation of 16 proteins, varying in size from 56 to 129 residues, yielded full-atom models that have 0.7-1.8 A root mean square deviations for the backbone atoms relative to the experimentally determined x-ray or NMR structures. The strategy also has been successfully applied in a blind manner to nine protein targets with molecular masses up to 15.4 kDa, whose conventional NMR structure determination was conducted in parallel by the Northeast Structural Genomics Consortium. This protocol potentially provides a new direction for high-throughput NMR structure determination.
authors.affiliation: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.forename: Oliver
authors.initials: O
authors.lastname: Lange
authors.forename: Frank
authors.initials: F
authors.lastname: Delaglio
authors.forename: Paolo
authors.initials: P
authors.lastname: Rossi
authors.forename: James M
authors.initials: JM
authors.lastname: Aramini
authors.forename: Gaohua
authors.initials: G
authors.lastname: Liu
authors.forename: Alexander
authors.initials: A
authors.lastname: Eletsky
authors.forename: Yibing
authors.initials: Y
authors.lastname: Wu
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Singarapu
authors.forename: Alexander
authors.initials: A
authors.lastname: Lemak
authors.forename: Alexandr
authors.initials: A
authors.lastname: Ignatchenko
authors.forename: Cheryl H
authors.initials: CH
authors.lastname: Arrowsmith
authors.forename: Thomas
authors.initials: T
authors.lastname: Szyperski
authors.forename: Gaetano T
authors.initials: GT
authors.lastname: Montelione
authors.forename: David
authors.initials: D
authors.lastname: Baker
authors.forename: Ad
authors.initials: A
authors.lastname: Bax
mesh_terms: D023281:Genomics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D012984:Software; D013816:Thermodynamics; D025801:Ubiquitin / Q000737:chemistry
chemical_list: D011506:Proteins; D025801:Ubiquitin