title: 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.
authors.affiliation: Department of Medicinal Chemistry, L.S. Skaggs Pharmacy Institute, University of Utah, 2000 East 30 South Skaggs 307, Salt Lake City, Utah 84112, USA.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Galindo-Murillo
authors.affiliation: Department of Medicinal Chemistry, L.S. Skaggs Pharmacy Institute, University of Utah, 2000 East 30 South Skaggs 307, Salt Lake City, Utah 84112, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Roe
authors.affiliation: Department of Medicinal Chemistry, L.S. Skaggs Pharmacy Institute, University of Utah, 2000 East 30 South Skaggs 307, Salt Lake City, Utah 84112, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Cheatham
mesh_terms: D004247:DNA / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D025341:Principal Component Analysis; D015203:Reproducibility of Results; D013997:Time Factors
chemical_list: D004247:DNA