Assessment of A- to B- DNA Transitions Utilizing the Drude Polarizable Force Field.

Abstract

In addition to the well-characterized B-form of DNA, duplex DNA can adopt various conformations, such as A or Z-DNA. Though less common, these structures can be induced biologically through protein or ligand interactions or experimentally with niche environmental conditions, such as high salt concentrations or in mixed water-ethanol. Reproducing these alternate structures through molecular dynamics simulations in recent years has been quite challenging with the currently available force fields, simulation techniques, and time scales. In this study, the Drude polarizable force field is tested for its ability to facilitate transitions between A-DNA and B-DNA or maintain A-DNA. Though transitions away from B-DNA were observed in high concentrations of ethanol, the resulting structures had hybrid properties taken from both B-DNA and A-DNA structures. This was also true for A-DNA in ethanol, which lost some of the A-DNA properties that it was expected to maintain. When B-DNA was tested in high salt environments, the resulting B-DNA structures showed no distinguishable differences with the increasing salt concentrations tested. These results with the Drude FF and recent results with additive force fields suggest that at present the current additive and polarizable force fields do not facilitate a complete transition between B- to A-DNA conformations under the conditions simulated. At present, the Drude FF favors A-B DNA hybrid structures when simulated in nonphysiological conditions.