Quantum mechanical study of vicinal J spin-spin coupling constants for the protein backbone

We have performed densisty functional theory (DFT) calculations of vicinal J coupling constants involving the backbone torsional angle for the protein GB3 using our recently developed automatic fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) approach (Xiao He et al. J. Phys. Chem. B 2009, 113, 10380-10388). Interestingly, the calculated values based on an NMR structure are more accurate than those based on a high-resolution X-ray strucure because the NMR structure was refined using a large number of residual dipolar couplings (RDCs) whereas the hydrogen atoms were added into the X-ray structure in idealized positions, confirming that the postioning of the hydrogen atoms relative to the backbone atoms is important to the accuracy of J coupling constant prediction. By comparing three Karplus equations, our results have demonstrated that hydrogen bonding, substituent and electrostatic effects could have significant impacts on vicinal J couplings even though they depend mostly on the intervening dihedral angles. The root-mean-square deviations (RMSDs) of the calculated ³J(H^N,H^α), ³J(H^N,C^β), ³J(H ^N,C′) values based on the NMR structure are 0.52, 0.25, and 0.35 Hz, respectively, after taking the dynamic effect into consideration. The excellent accuracy demonstrates that our AF-QM/MM approach is a useful tool to study the relationship between J coupling constants and the structure and dynamics of proteins.