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 ϕ/ψ torsion angles seen in intrinsically disordered proteins (IDPs). The ϕ/ψ torsion angle distribution of the library, on average, provides good agreement with experimentally observed chemical shifts and 3J HN‐Hα coupling constants for a set of five disordered proteins. Inspection of the coil library confirms that nearest‐neighbor effects significantly impact the ϕ/ψ distribution of residues in the coil state. Importantly, 3J HN‐Hα coupling constants derived from the nearest‐neighbor modulated backbone ϕ distribution in the coil library show improved agreement to experimental values, thereby providing a better way to predict 3J HN‐Hα coupling constants for IDPs, and for identifying locations that deviate from fully random behavior.