title: Characterization of the residual structure in the unfolded state of the Delta131Delta fragment of staphylococcal nuclease.
abstract: The determination of the conformational preferences in unfolded states of proteins constitutes an important challenge in structural biology. We use inter-residue distances estimated from site-directed spin-labeling NMR experimental measurements as ensemble-averaged restraints in all-atom molecular dynamics simulations to characterise the residual structure of the Delta131Delta fragment of staphylococcal nuclease under physiological conditions. Our findings indicate that Delta131Delta under these conditions shows a tendency to form transiently hydrophobic clusters similar to those present in the native state of wild-type staphylococcal nuclease. Only rarely, however, all these interactions are simultaneously realized to generate conformations with an overall native topology.
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Francis
authors.forename: Kresten
authors.initials: K
authors.lastname: Lindorff-Larsen
authors.forename: Robert B
authors.initials: RB
authors.lastname: Best
authors.forename: Michele
authors.initials: M
authors.lastname: Vendruscolo
mesh_terms: D003198:Computer Simulation; D057927:Hydrophobic and Hydrophilic Interactions; D008836:Micrococcal Nuclease / Q000737:chemistry*; D009010:Monte Carlo Method; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry*; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary
chemical_list: D010446:Peptide Fragments; D008836:Micrococcal Nuclease