title: Direct Investigation of Slow Correlated Dynamics in Proteins via Dipolar Interactions.
abstract: The synchronization of native state motions as they transition between microstates influences catalysis kinetics, mediates allosteric interactions, and reduces the conformational entropy of proteins. However, it has proven difficult to describe native microstates because they are usually minimally frustrated and may interconvert on the micro- to millisecond time scale. Direct observation of concerted equilibrium fluctuations would therefore be an important tool for describing protein native states. Here we propose a strategy that relates NMR cross-correlated relaxation (CCR) rates between dipolar interactions to residual dipolar couplings (RDCs) of individual consecutive H(N)-N and H(α)-C(α) bonds, which act as a proxy for the peptide planes and the side chains, respectively. Using Xplor-NIH ensemble structure calculations restrained with the RDC and CCR data, we observe collective motions on time scales slower than nanoseconds in the backbone for GB3. To directly access the correlations from CCR, we develop a structure-free data analysis. The resulting dynamic correlation map is consistent with the ensemble-restrained simulations and reveals a complex network. In general, we find that the bond motions are on average slightly correlated and that the local environment dominates many observations. Despite this, some patterns are typical over entire secondary structure elements. In the β-sheet, nearly all bonds are weakly correlated, and there is an approximately binary alternation in correlation intensity corresponding to the solvent exposure/shielding alternation of the side chains. For α-helices, there is also a weak correlation in the H(N)-N bonds. The degree of correlation involving H(α)-C(α) bonds is directly affected by side-chain fluctuations, whereas loops show complex and nonuniform behavior.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona) , Parc Científic de Barcelona, C/Baldiri Reixac 10, 08028 Barcelona, Spain.|The Scripps Research Institute (TSRI) , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: R Bryn
authors.initials: RB
authors.lastname: Fenwick
authors.affiliation: Division of Computational Bioscience, Center for Information Technology, National Institutes of Health , Building 12A, Bethesda, Maryland 20892-5624, United States.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Schwieters
authors.affiliation: Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH-Hönggerberg , Vladimir-Prelog-Weg 2, CH-8093 Zürich, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Vögeli
mesh_terms: D007700:Kinetics; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D012997:Solvents / Q000737:chemistry
chemical_list: D011506:Proteins; D012997:Solvents