Prediction of nearest neighbor effects on backbone torsion angles and NMR scalar coupling constants in disordered proteins

Using fine-tuned hydrogen bonding criteria, a library of coiled peptide fragments has been generated from a large set of high-resolution protein X-ray structures. This library is shown to be an improved representation of phi/ torsion angles seen in intrinsically disordered proteins (IDPs). The phi/ torsion angle distribution of the library, on average, provides good agreement with experimentally observed chemical shifts and (3)J(HN-H) coupling constants for a set of five disordered proteins. Inspection of the coil library confirms that nearest-neighbor effects significantly impact the phi/ distribution of residues in the coil state. Importantly, (3)J(HN-H) coupling constants derived from the nearest-neighbor modulated backbone phi distribution in the coil library show improved agreement to experimental values, thereby providing a better way to predict (3)J(HN-H) coupling constants for IDPs, and for identifying locations that deviate from fully random behavior.