Molecular properties from combined QM/MM methods. 2. Chemical shifts in large molecules

A method for calculating the chemical shielding tensor of any atom with the QM/MM approach has been developed. The method is described and applied to a number of model systems including the water dimer, NMA-water complexes, c ytosine monophosphate, paired and stacked nucleic acid bases, imidazole-met al complexes, and 1'-deoxyribose-metal ion complexes. The results demonstra te that with an appropriate QM/MM partition, good descriptions of the envir onmental effects on chemical shift tensors are obtained. The typical error compared to full QM calculations is 1-2 ppm for heavy atoms. At distances b elow 2.5 Angstrom, such as occur in hydrogen bonding, larger errors arise d ue to the lack of Pauli repulsion and magnetic susceptibility of the nearby groups in the current QM/MM model; including the hydrogen bonded molecules as part of the QM region is a way of solving this problem. The method is a lso applied to a simple model of myoglobin-CO and it is shown that the sign ificant influence from the distal histidine on the shielding of Fe and CO i s well reproduced by a QM/MM calculation. Application to the chemical shift of the 1-N nitrogen in nicotinamide adenine dinucleotide (NAD(+)), relativ e to N-methyl nicotinamide, gives good results, indicating that accurate ch emical shifts can be obtained for specific atoms in large molecules that ca nnot be treated by QM at the MP2 level. The effect of solvation on the chem ical shift of water was also studied with the QM/MM approach in a molecular dynamics framework. The test calculations described in this paper demonstr ate that the QM/MM method for estimating shielding tensors and chemical shi fts is a useful approach for large systems.