Quantitative Description of Backbone Conformational Sampling of Unfolded Proteins at Amino Acid Resolution from NMR Residual Dipolar Couplings

An atomic resolution characterization of the structural properties of unfolded proteins that explicitly invokes the highly dynamic nature of the unfolded state will be extremely important for the development of a quantitative understanding of the thermodynamic basis of protein folding and stability. Here we develop a novel approach using residual dipolar couplings (RDCs) from unfolded proteins to determine conformational behavior on an amino acid specific basis. Conformational sampling is described in terms of ensembles of structures selected from a large pool of conformers. We test this approach, using extensive simulation, to determine how well the fitting of RDCs to reduced conformational ensembles containing few copies of the molecule can correctly reproduce the backbone conformational behavior of the protein. Having established approaches that allow accurate mapping of backbone dihedral angle conformational space from RDCs, we apply these methods to obtain an amino acid specific description of ubiqui...