Quantum chemical modeling of through-hydrogen bond spin-spin coupling in amides and ubiquitin

Through-hydrogen bond spin-spin coupling has been investigated computationally in the formamide dimer and in fragments of the protein ubiquitin. The Fermi-contact term was calculated by finite perturbation theory with the B3LYP DFT method with several basis sets. The distance and angular dependence of the 3J(N,C') coupling constant (N-H--O=C) in the hydrogen-bonded formamide dimer was firstly examined for a wide range of mutual arrangements, also in relation to the stability of the dimer. The magnitude of 3J(N,C') is relatively insensitive to the dihedral angle between the two amide planes, whereas values between 1-2 Hz are calculated for a variety of arrangements, including non-linear hydrogen bonds, in agreement with the shape of some occupied, low-lying molecular orbitals which connect donor and acceptor. Then, fragments of the ubiquitin protein (for which such coupling constants are experimentally available) were generated by removing from the experimental structure all amino acids except those involved in hydrogen bonding, and coupling constants were calculated for such fragments. Although calculated 3J(N,C') values are sometimes overestimated, they generally correlate with the corresponding experimental values.