Ab initio and density functional theory studies of nuclear magnetic resonance and electron spin resonance parameters of biomolecules

NMR chemical shifts are sensitive indicators for conformations of proteins and other macromolecules. To assess the accuracy of the chemical shift calculations by modern quantum chemistry, we have calculated proton chemical shifts for a series of aromatic molecules at different theoretical levels (Hartree-Fock, Density Functional Theory, and second-order Møller-Plesset (MP2) Theory) and compared these values with carefully re-measured experimental values. All tested methods give excellent performance. The best agreement is obtained at the B3LYP/6-311++G** level with an RMSD of 0.037 ppm. The results show that it is possible, at a reasonable cost, to calculate relative proton shieldings in a similar chemical environment to high accuracy. Next, the proton chemical shifts of a set of cyclic amide compounds were measured in both DMSO and D ₂O solutions, and compared to their theoretical values. The agreements after linear regression for both solutions are good enough to reach a predictive accuracy of 0.1∼0.3 ppm. Thus we can use the calculated gas phase proton chemical shifts directly to predict experimental data in various solvents, including water.; Conformations of BKM-824, a cyclic bradykinin antagonist mimic, have been studied by comparing the calculated 1H, 13C and 19F chemical shifts with experimental values. The NMR backbone structure is confirmed by well-reproduced chemical shifts at those positions. Some sidechain conformations are refined by this comparison.; The C-HO interaction between N-methyl maleimide (NMM) and DMSO has been detected by the NMR spectra at different temperatures. Theoretical calculations show that the NMM-DMSO complex tends to form a bifurcated hydrogen bond. Nature of this interaction has been studied by the calculation of binding energy and NMR chemical shifts at and around the equilibrium geometry.; A new gaussian-weighted operator for calculating hyperfine coupling constants is implemented in the Density Functional Theory. The tests on some free atoms, diatomic and polyatomic molecules show that the combination of the new operator and DFT provides a useful tool to calculate this challenging property.