BI and BII conformational sub states in the DNA backbone typify canonical B-form DNA. The BI and BII sub states are important for structural variation of DNA and have been implicated protein-nucleic acid recognition mechanisms. Recent refinements have been made to nucleic acid force fields employed in molecular dynamics simulations that demonstrate a better ability to model the BI and BII states, leading to overall improved modeling of DNA structure and dynamics. These force field improvements have yet to be significantly demonstrated in the context of a protein-DNA system extended to long time scales. Our plan was to run molecular dynamics simulations of a well-studied protein-DNA system (E2-DNA) into the microsecond time scale and determine the ability of the force field to populate BII states in the DNA backbone consistent with dinucleotide steps crystallized in the BII conformation. The results showed that the dinucleotide steps in the E2-DNA complex with the highest BII populations from simulation trajectories corresponded to the dinucleotide steps crystallized in the BII state and that decoy BI and BII states converge to the same results within approximately one microsecond. This is an important step on the way to understanding protein-DNA recognition mechanisms that involve DNA backbone polymorphisms. Additional simulations are underway to explore DNA backbone dynamics of the protein-DNA recognition mechanism and the role dynamics play in indirect readout interactions. This requires the development of new methods to efficiently sample complex interactions at the protein-DNA interface. These new methods are suited to study protein-DNA interactions on large, massively parallel machines equipped with GPU accelerators such as Blue Waters.

DNA backbone BI/BII sub-state distribution and dynamics in protein-bound environment determined by molecular dynamics simulations

251st National Meeting (2016)

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