On the absence of intrahelical DNA dynamics on the μs to ms timescale

Abstract

DNA helices display a rich tapestry of motion on both short (<100 ns) and long (>1 ms) timescales. However, with the exception of mismatched or damaged DNA, experimental measures indicate that motions in the 1 μs to 1 ms range are effectively absent, which is often attributed to difficulties in measuring motions in this time range. We hypothesized that these motions have not been measured because there is effectively no motion on this timescale, as this provides a means to distinguish faithful Watson-Crick base-paired DNA from damaged DNA. The absence of motion on this timescale would present a 'static' DNA sequence-specific structure that matches the encounter timescales of proteins, thereby facilitating recognition. Here we report long-timescale (∼10-44 μs) molecular dynamics simulations of a B-DNA duplex structure that addresses this hypothesis using both an 'Anton' machine and large ensembles of AMBER GPU simulations.