Fragment density functional theory calculation of NMR chemical shifts for proteins with implicit solvation

Fragment density functional theory (DFT) calculation of NMR chemical shifts for several proteins (Trp-cage, Pin1 WW domain, the third IgG-binding domain of Protein G (GB3) and human ubiquitin) has been carried out. The present study is based on a recently developed automatic fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) approach but the solvent effects are included by using the PB (Poisson-Boltzmann) model. Our calculated chemical shifts of ¹H and ¹³C for these four proteins are in excellent agreement with experimentally measured values and represent clear improvement over that from the gas phase calculation. However, although the inclusion of the solvent effect also improves the computed chemical shifts of ¹⁵N, the results do not agree with experimental values as well as ¹H and ¹³C. Our study also demonstrates that AF-QM/MM calculated results accurately reproduce the separation of α-helical and β-sheet chemical shifts for ¹³C _α atoms in proteins, and using the ¹H chemical shift to discriminate the native structure of proteins from decoys is quite remarkable.