A Fast QM/MM (Quantum Mechanical/Molecular Mechanical) Approach to Calculate Nuclear Magnetic Resonance Chemical Shifts for Macromolecules.

A fast approach to calculate nuclear magnetic resonance (NMR) chemical shifts within the quantum mechanical/molecular mechanical (QM/MM) framework has been developed. The QM treatment is based on our recently implemented MNDO/NMR method (Wang et al. J. Chem. Phys. 2004, 120, 11392). The effect of the QM/MM partitioning on chemical shifts has been investigated by test calculations on the water dimer and on the protein crambin. It has been shown that the quantum mechanical treatment of the hydrogen bond and nearby groups with significant magnetic susceptibilities is necessary in order to reproduce the full QM results. The method is also applied to a protein-ligand complex FKBP-GPI, and excellent agreement for proton chemical shifts of the ligand is obtained by including the side-chain atoms of the binding site residues into the QM region. The NMR chemical shift calculations using QM/MM-minimized structures still yield satisfactory results. Our results demonstrate that this QM/MM NMR method is able to treat critical regions of very large macromolecules without compromising accuracy if a relatively large QM region is used.