A computational protocol for 15N NMR parameter prediction in aqueous peptide ensembles using optimized DFT methods

Abstract

Accurate prediction of ¹⁵N NMR chemical shifts in flexible peptide systems remains challenging. We present an ensemble-based computation protocol combining density functional theory with replica-exchange molecular dynamics. This approach outperformed single-structure predictions with deviations of 2.5–5.6 ppm for most residues and 1.1 ppm for leucine in a model peptide.