title: Lennard-Jones Parameters for B3LYP/CHARMM27 QM/MM Modeling of Nucleic Acid Bases.
abstract: Combined quantum mechanics/molecular mechanics (QM/MM) methods allow computations on chemical events in large molecular systems. Here, we have tested the suitability of the standard CHARMM27 forcefield Lennard-Jones van der Waals (vdW) parameters for the treatment of nucleic acid bases in QM/MM calculations at the B3LYP/6-311+G(d,p)-CHARMM27 level. Alternative parameters were also tested by comparing the QM/MM hydrogen bond lengths and interaction energies with full QM [B3LYP/6-311+G(d,p)] results. The optimization of vdW parameters for nucleic acid bases is challenging because of the likelihood of multiple hydrogen bonds between the nucleic acid base and a water molecule. Two sets of optimized atomic vdW parameters for polar hydrogen, carbonyl carbon, and aromatic nitrogen atoms for nucleic acid bases are reported: base-dependent and base-independent. The results indicate that, for QM/MM investigations of nucleic acids, the standard forcefield vdW parameters may not be appropriate for atoms treated by QM. QM/MM interaction energies calculated with standard CHARMM27 parameters are found to be too large, by around 3 kcal/mol. This is because of overestimation of electrostatic interactions. Interaction energies closer to the full QM results are found using the optimized vdW parameters developed here. The optimized vdW parameters [developed by reference to B3LYP/6-311+G(d,p) results] were also tested at the B3LYP/6-31G(d) QM/MM level and were found to be transferable to the lower level. The optimized parameters also model the interaction energies of charged nucleic acid bases and deprotonation energies reasonably well.
authors.affiliation: Centre for Computational Chemistry, School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, United Kingdom, and Department of Biological and Environmental Science and NanoScience Center, University of Jyväskylä, P.O. Box 35, 40014 Jyväskylä, Finland.
authors.forename: Ulla
authors.initials: U
authors.lastname: Pentikäinen
authors.affiliation: Centre for Computational Chemistry, School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, United Kingdom, and Department of Biological and Environmental Science and NanoScience Center, University of Jyväskylä, P.O. Box 35, 40014 Jyväskylä, Finland.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Shaw
authors.affiliation: Centre for Computational Chemistry, School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, United Kingdom, and Department of Biological and Environmental Science and NanoScience Center, University of Jyväskylä, P.O. Box 35, 40014 Jyväskylä, Finland.
authors.forename: Kittusamy
authors.initials: K
authors.lastname: Senthilkumar
authors.affiliation: Centre for Computational Chemistry, School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, United Kingdom, and Department of Biological and Environmental Science and NanoScience Center, University of Jyväskylä, P.O. Box 35, 40014 Jyväskylä, Finland.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Woods
authors.affiliation: Centre for Computational Chemistry, School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, United Kingdom, and Department of Biological and Environmental Science and NanoScience Center, University of Jyväskylä, P.O. Box 35, 40014 Jyväskylä, Finland.
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Mulholland