title: Ensemble models of proteins and protein domains based on distance distribution restraints.
abstract: Conformational ensembles of intrinsically disordered peptide chains are not fully determined by experimental observations. Uncertainty due to lack of experimental restraints and due to intrinsic disorder can be distinguished if distance distributions restraints are available. Such restraints can be obtained from pulsed dipolar electron paramagnetic resonance (EPR) spectroscopy applied to pairs of spin labels. Here, we introduce a Monte Carlo approach for generating conformational ensembles that are consistent with a set of distance distribution restraints, backbone dihedral angle statistics in known protein structures, and optionally, secondary structure propensities or membrane immersion depths. The approach is tested with simulated restraints for a terminal and an internal loop and for a protein with 69 residues by using sets of sparse restraints for underlying well-defined conformations and for published ensembles of a premolten globule-like and a coil-like intrinsically disordered protein.
authors.affiliation: ETH Zürich, Laboratory of Physical Chemistry, Department of Chemistry and Applied Biosciences, Zürich, 8093, Switzerland.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Jeschke
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D051357:Cyclin-Dependent Kinase 2 / Q000737:chemistry*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D008958:Models, Molecular; D009010:Monte Carlo Method; D011485:Protein Binding; D000072417:Protein Domains; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013113:Spin Labels
chemical_list: C436291:CDKN1B protein, human; D064267:Intrinsically Disordered Proteins; D013113:Spin Labels; D050760:Cyclin-Dependent Kinase Inhibitor p27; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2
keywords: EPR spectroscopy; NMR spectroscopy; intrinsically disordered domains; intrinsically disordered proteins; membrane proteins; mixed resolution; statistical coil