title: Transitions of Double-Stranded DNA Between the A- and B-Forms.
abstract: The structure of double-stranded DNA (dsDNA) is sensitive to solvent conditions. In solution, B-DNA is the favored conformation under physiological conditions, while A-DNA is the form found under low water activity. The A-form is induced locally in some protein-DNA complexes, and repeated transitions between the B- and A-forms have been proposed to generate the forces used to drive dsDNA into viral capsids during genome packaging. Here, we report analyses on previous molecular dynamics (MD) simulations on B-DNA, along with new MD simulations on the transition from A-DNA to B-DNA in solution. We introduce the A-B Index (ABI), a new metric along the A-B continuum, to quantify our results. When A-DNA is placed in an equilibrated solution at physiological ionic strength, there is no energy barrier to the transition to the B-form, which begins within about 1 ns. The transition is essentially complete within 5 ns, although occasionally a stretch of a few base pairs will remain A-like for up to ∼10 ns. A comparison of four sequences with a range of predicted A-phobicities shows that more A-phobic sequences make the transition more rapidly than less A-phobic sequences. Simulations on dsDNA with a region of roughly one turn locked in the A-form allow us to characterize the A/B junction, which has an average bend angle of 20-30°. Fluctuations in this angle occur with characteristic times of about 10 ns.
authors.affiliation: School of Physics, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
authors.forename: James T
authors.initials: JT
authors.lastname: Waters
authors.affiliation: Department of Biological Sciences, Columbia University , New York, New York 10027, United States.
authors.forename: Xiang-Jun
authors.initials: XJ
authors.lastname: Lu
authors.affiliation: Department of Medicinal Chemistry, L.S. Skaggs Pharmacy Institute, University of Utah , Salt Lake City, Utah 84112, United States.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Galindo-Murillo
authors.affiliation: School of Physics, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
authors.forename: James C
authors.initials: JC
authors.lastname: Gumbart
authors.affiliation: School of Physics, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
authors.forename: Harold D
authors.initials: HD
authors.lastname: Kim
authors.affiliation: Department of Medicinal Chemistry, L.S. Skaggs Pharmacy Institute, University of Utah , Salt Lake City, Utah 84112, United States.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Cheatham
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Harvey
mesh_terms: D044704:DNA, A-Form / Q000737:chemistry / Q000378:metabolism*; D059371:DNA, B-Form / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D012965:Sodium Chloride / Q000737:chemistry; D012996:Solutions / Q000737:chemistry; D012997:Solvents / Q000737:chemistry
chemical_list: D044704:DNA, A-Form; D059371:DNA, B-Form; D012996:Solutions; D012997:Solvents; D012965:Sodium Chloride