title: Experimental Protein Structure Verification by Scoring with a Single, Unassigned NMR Spectrum.
abstract: Standard methods for de novo protein structure determination by nuclear magnetic resonance (NMR) require time-consuming data collection and interpretation efforts. Here we present a qualitatively distinct and novel approach, called Comparative, Objective Measurement of Protein Architectures by Scoring Shifts (COMPASS), which identifies the best structures from a set of structural models by numerical comparison with a single, unassigned 2D (13)C-(13)C NMR spectrum containing backbone and side-chain aliphatic signals. COMPASS does not require resonance assignments. It is particularly well suited for interpretation of magic-angle spinning solid-state NMR spectra, but also applicable to solution NMR spectra. We demonstrate COMPASS with experimental data from four proteins--GB1, ubiquitin, DsbA, and the extracellular domain of human tissue factor--and with reconstructed spectra from 11 additional proteins. For all these proteins, with molecular mass up to 25 kDa, COMPASS distinguished the correct fold, most often within 1.5 Å root-mean-square deviation of the reference structure.
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Courtney
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Nesbitt
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Tang
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Tuttle
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Watt
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Nuzzio
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Lindsay J
authors.initials: LJ
authors.lastname: Sperling
authors.affiliation: Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Gemma
authors.initials: G
authors.lastname: Comellas
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Peterson
authors.affiliation: Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Morrissey
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: rienstra@illinois.edu.
authors.forename: Chad M
authors.initials: CM
authors.lastname: Rienstra
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002247:Carbon Isotopes; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D019704:Protein Disulfide-Isomerases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012107:Research Design; D012984:Software; D013291:Streptococcus / Q000737:chemistry; D040681:Structural Homology, Protein; D013925:Thromboplastin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D002247:Carbon Isotopes; D029968:Escherichia coli Proteins; C034284:IgG Fc-binding protein, Streptococcus; D011994:Recombinant Proteins; D025801:Ubiquitin; D013925:Thromboplastin; D019704:Protein Disulfide-Isomerases; C526648:dsbA protein, E coli