Quantum Mechanics/Molecular Mechanics Free Energy Maps and Nonadiabatic Simulations for a Photochemical Reaction in DNA: Cyclobutane Thymine Dimer

J Phys Chem Lett. 2016 Nov 3;7(21):4391-4397. doi: 10.1021/acs.jpclett.6b02168. Epub 2016 Oct 25.


The absorption of ultraviolet radiation by DNA may result in harmful genetic lesions that affect DNA replication and transcription, ultimately causing mutations, cancer, and/or cell death. We analyze the most abundant photochemical reaction in DNA, the cyclobutane thymine dimer, using hybrid quantum mechanics/molecular mechanics (QM/MM) techniques and QM/MM nonadiabatic molecular dynamics. We find that, due to its double helix structure, DNA presents a free energy barrier between nonreactive and reactive conformations leading to the photolesion. Moreover, our nonadiabatic simulations show that most of the photoexcited reactive conformations return to standard B-DNA conformations after an ultrafast nonradiative decay to the ground state. This work highlights the importance of dynamical effects (free energy, excited-state dynamics) for the study of photochemical reactions in biological systems.

Publication types

  • Letter

MeSH terms

  • Cyclobutanes / chemistry*
  • Molecular Dynamics Simulation
  • Photochemical Processes
  • Pyrimidine Dimers / chemistry*
  • Quantum Theory*


  • Cyclobutanes
  • Pyrimidine Dimers