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Dynamical Recrossing in the Intercalation Process of the Anticancer Agent Proflavine into DNA

V M Hridya1, James T Hynes2,3, Arnab Mukherjee1

  • 1Department of Chemistry , Indian Institute of Science Education and Research , Pune 411008 , India.

The Journal of Physical Chemistry. B
|November 1, 2019
PubMed

Insights

This study reveals that DNA intercalation dynamics, using proflavine as a model, significantly deviate from traditional transition state theory (TST). Novel methods are needed to understand these complex biomolecular processes.

Area of Science:

  • Molecular Biophysics
  • Computational Chemistry
  • Pharmacology

Background:

  • DNA intercalation is a key mechanism for certain antibiotics.
  • Previous studies focused on static free energy landscapes.
  • Understanding dynamical effects is crucial for drug design.

Purpose of the Study:

  • To investigate the dynamical effects in proflavine-DNA intercalation.
  • To calculate the transmission coefficient (κ) and assess deviations from transition state theory (TST).
  • To evaluate the applicability of existing theories (Grote-Hynes, Kramers) to this complex system.

Main Methods:

  • All-atom simulations totaling 6.3 ms to identify the transition state via committor analysis.
  • Extensive simulations to calculate the transmission coefficient (κ).
  • Comparison of results with Grote-Hynes and Kramers theories.

Main Results:

  • A small transmission coefficient (κ = 0.1) was found, indicating significant departure from TST.
  • Neither Grote-Hynes nor Kramers theories accurately captured the system's recrossing events.
  • The study highlights the complexity of dynamical effects in biomolecular processes.

Conclusions:

  • Dynamical effects in DNA intercalation are complex and deviate significantly from TST predictions.
  • Current theoretical models are insufficient for describing the recrossing dynamics of such systems.
  • Novel computational approaches are required to fully elucidate these biomolecular mechanisms.

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