Are accurate computations of the 13C′ shielding feasible at the DFT level of theory?

摘要

The goal of this study is twofold. First, to investigate the relative influence of the main structural factors affecting the computation of the ¹³C′ shielding, namely, the conformation of the residue itself and the next nearest-neighbor effects. Second, to determine whether calculation of the ¹³C′ shielding at the DFT level of theory, with an accuracy similar to that of the ¹³C^α shielding, is feasible with the existing computational resources. The DFT calculations, carried out for a large number of possible conformations of the tripeptide Ac-G>XY-NMe, with different combinations of >X and >Y residues, enable us to conclude that the accurate computation of the ¹³C′ shielding for a given residue >X depends on the: (i) (φ,ψ) backbone torsional angles of >X; (ii) side-chain conformation of >X; (iii) (φ,ψ) torsional angles of >Y; and (iv) identity of residue >Y. Consequently, DFT-based quantum mechanical calculations of the ¹³C′ shielding, with all these factors taken into account, are two orders of magnitude more CPU demanding than the computation, with similar accuracy, of the ¹³C^α shielding. Despite not considering the effect of the possible hydrogen bond interaction of the carbonyl oxygen, this work contributes to our general understanding of the main structural factors affecting the accurate computation of the ¹³C′ shielding in proteins and may spur significant progress in effort to develop new validation methods for protein structures.