Lennard-Jones Parameters for B3LYP/CHARMM27 QM/MM Modeling of Nucleic Acid Bases

Ulla Pentikainen*, Katherine E. Shaw, Kittusamy Senthilkumar, Christopher J. Woods, Adrian J. Mulholland

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)396-410
Number of pages15
JournalJournal of Chemical Theory and Computation
Volume5
Issue number2
DOIs
Publication statusPublished - Feb 2009

Keywords

  • AB-INITIO QM/MM
  • ORBITAL GHO METHOD
  • MOLECULAR-DYNAMICS SIMULATIONS
  • CHEMICAL ACCURACY
  • COMBINED QUANTUM
  • NONENZYMATIC HYDROLYSIS
  • PHOSPHODIESTER BOND
  • ORGANIC-MOLECULES
  • EMPIRICAL FORCE-FIELD
  • SINGLE-STRANDED OLIGORIBONUCLEOTIDES

Cite this