Effects of dynamics and environment on N-15 chemical shielding anisotropy in proteins. A combination of density functional theory, molecular dynamicssimulation, and NMR relaxation

The interpretation of nuclear spin relaxation data of biomolecules often re quires the accurate knowledge of chemical shielding anisotropy (CSA) tensor s, which significantly depend on the environment and on intramolecular dyna mics. CSA tensors are studied in this work by density functional theory and by molecular dynamics simulations. It is demonstrated that density functio nal theory yields CSA tensors for N-15 nuclei in the side chain of crystall ine asparagine and in the peptide bond of crystalline alanine-alanine dipep tide with an accuracy comparable to that of solid-state NMR. In these calcu lations, the molecular fragment containing the nucleus of interest is treat ed with an IGLO-II and IGLO-III basis set while neighboring fragments exhib iting close contacts are represented by a DZVP set. In addition, electrosta tic effects are taken into account by explicit partial point charges. The d ynamical averaging of CSA tensors is investigated by applying density funct ional theory to snapshots of a molecular dynamics trajectory of the protein ubiquitin. The fluctuation properties of the N-15 CSA tensors of two gluta mine side chains are assessed. Computed auto- and cross-correlated relaxati on parameters using these CSA tensors are found to be in good agreement wit h the experiment. Local charges and close contacts can have a significant e ffect on N-15 CSA tensors and have to be taken into account when transferri ng CSA parameters from model compounds to proteins.