Induced polarization influences the fundamental forces in DNA base flipping

Justin A. Lemkul, Alexey Savelyev, Alexander D. MacKerell

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Base flipping in DNA is an important process involved in genomic repair and epigenetic control of gene expression. The driving forces for these processes are not fully understood, especially in the context of the underlying dynamics of the DNA and solvent effects. We studied double-stranded DNA oligomers that have been previously characterized by imino proton exchange NMR using both additive and polarizable force fields. Our results highlight the importance of induced polarization on the base flipping process, yielding near-quantitative agreement with experimental measurements of the equilibrium between the base-paired and flipped states. Further, these simulations allow us to quantify for the first time the energetic implications of polarization on the flipping pathway. Free energy barriers to base flipping are reduced by changes in dipole moments of both the flipped bases that favor solvation of the bases in the open state and water molecules adjacent to the flipping base.

Original languageEnglish
Pages (from-to)2077-2083
Number of pages7
JournalJournal of Physical Chemistry Letters
Volume5
Issue number12
DOIs
StatePublished - Jun 19 2014

Keywords

  • CHARMM
  • base opening
  • force field
  • molecular dynamics
  • nucleic acids
  • polarizability
  • potential of mean force

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