title: Structure Calculation and Reconstruction of Discrete-State Dynamics from Residual Dipolar Couplings.
abstract: Residual dipolar couplings (RDCs) acquired by nuclear magnetic resonance (NMR) spectroscopy are an indispensable source of information in investigation of molecular structures and dynamics. Here, we present a comprehensive strategy for structure calculation and reconstruction of discrete-state dynamics from RDC data that is based on the singular value decomposition (SVD) method of order tensor estimation. In addition to structure determination, we provide a mechanism of producing an ensemble of conformations for the dynamical regions of a protein from RDC data. The developed methodology has been tested on simulated RDC data with ±1 Hz of error from an 83 residue α protein (PDB ID 1A1Z ) and a 213 residue α/β protein DGCR8 (PDB ID 2YT4 ). In nearly all instances, our method reproduced the structure of the protein including the conformational ensemble to within less than 2 Å. On the basis of our investigations, arc motions with more than 30° of rotation are identified as internal dynamics and are reconstructed with sufficient accuracy. Furthermore, states with relative occupancies above 20% are consistently recognized and reconstructed successfully. Arc motions with a magnitude of 15° or relative occupancy of less than 10% are consistently unrecognizable as dynamical regions within the context of ±1 Hz of error.
authors.affiliation: Department of Computer Science & Engineering, University of South Carolina , Columbia, South Carolina 29208, United States.
authors.forename: Casey A
authors.initials: CA
authors.lastname: Cole
authors.affiliation: Department of Computer Science & Engineering, University of South Carolina , Columbia, South Carolina 29208, United States.
authors.forename: Rishi
authors.initials: R
authors.lastname: Mukhopadhyay
authors.affiliation: Department of Computer Science & Engineering, University of South Carolina , Columbia, South Carolina 29208, United States.
authors.forename: Hanin
authors.initials: H
authors.lastname: Omar
authors.affiliation: Nutrition Research Institute, University of North Carolina at Chapel Hill , Kannapolis, North Carolina 27514, United States.
authors.forename: Mirko
authors.initials: M
authors.lastname: Hennig
authors.affiliation: Department of Computer Science & Engineering, University of South Carolina , Columbia, South Carolina 29208, United States.
authors.forename: Homayoun
authors.initials: H
authors.lastname: Valafar
mesh_terms: D053200:Fas-Associated Death Domain Protein / Q000737:chemistry*; D006801:Humans; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D016601:RNA-Binding Proteins / Q000737:chemistry*
chemical_list: C474043:DGCR8 protein, human; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D016601:RNA-Binding Proteins