CHARMM Drude Polarizable MD Simulations Reproduce Solution X-ray Diffraction Patterns for B-DNA Sequences and Predict Differential Impact of the Li+, Na+, K+ and Rb+ Ions on DNA Conformational Properties

Alexey Sayelyev (School of Pharmacy, University of Maryland)

I will talk about development of the first generation CHARMM Drude polarizable force field for DNA, which is capable of reproducing the main conformational features of DNA in solution, such as A-to-B equilibrium and transitions between BI and BII substates. Our current efforts are directed towards further model improvement, by achieving a proper balance of the interactions among surrounding mobile ions, water and DNA. Compared to the additive (non-polarizable) models, explicit treatment of the electronic polarizability in the Drude model leads to a markedly improved description of the interplay between the ionic atmosphere and DNA conformational behavior. In particular, the Drude model is shown to more accurately reproduce counterion condensation theory predictions of DNA charge neutralization by condensed ions, as well as the experimental data on the competitive binding of Li+, Na+, K+ and Rb+ ions to DNA. The most intriguing results is that the model predicts a differential impact of these seemingly similar monovalent cations on DNA conformational properties - a phenomenon not observed in the state-of-the-art CHARMM36 and AMBER atomistic additive models. In addition, the Drude model reproduces the solution X-ray diffraction patterns for a number of B form DNA sequences at a level of accuracy similar to, or exceeding that of the above mentioned additive models. The obtained results indicate that CHARMM Drude polarizable MD simulations provide a more realistic model of the physical forces involved in the interactions of DNA with its ionic environment, offering the potential to yield new insights into salt-mediated biological processes involving DNA, such as protein-DNA recognition and chromatin folding.

Back to Seminar Home Page

Last modified 12-November-2014 by website owner: NCNR (attn: )