title: Why double-stranded RNA resists condensation.
abstract: The addition of small amounts of multivalent cations to solutions containing double-stranded DNA leads to inter-DNA attraction and eventual condensation. Surprisingly, the condensation is suppressed in double-stranded RNA, which carries the same negative charge as DNA, but assumes a different double helical form. Here, we combine experiment and atomistic simulations to propose a mechanism that explains the variations in condensation of short (25 base-pairs) nucleic acid (NA) duplexes, from B-like form of homopolymeric DNA, to mixed sequence DNA, to DNA:RNA hybrid, to A-like RNA. Circular dichroism measurements suggest that duplex helical geometry is not the fundamental property that ultimately determines the observed differences in condensation. Instead, these differences are governed by the spatial variation of cobalt hexammine (CoHex) binding to NA. There are two major NA-CoHex binding modes--internal and external--distinguished by the proximity of bound CoHex to the helical axis. We find a significant difference, up to 5-fold, in the fraction of ions bound to the external surfaces of the different NA constructs studied. NA condensation propensity is determined by the fraction of CoHex ions in the external binding mode.
authors.affiliation: Department of Computer Science, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Igor S
authors.initials: IS
authors.lastname: Tolokh
authors.affiliation: School of Applied and Engineering Physics, Cornell University, Ithaca, NY 14853-3501, USA.
authors.forename: Suzette A
authors.initials: SA
authors.lastname: Pabit
authors.affiliation: School of Applied and Engineering Physics, Cornell University, Ithaca, NY 14853-3501, USA.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Katz
authors.affiliation: School of Applied and Engineering Physics, Cornell University, Ithaca, NY 14853-3501, USA.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Physics, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Drozdetski
authors.affiliation: Applied Statistics and Computational Modeling Group, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Baker
authors.affiliation: School of Applied and Engineering Physics, Cornell University, Ithaca, NY 14853-3501, USA lp26@cornell.edu.
authors.forename: Lois
authors.initials: L
authors.lastname: Pollack
authors.affiliation: Department of Computer Science, Virginia Tech, Blacksburg, VA 24061, USA Department of Physics, Virginia Tech, Blacksburg, VA 24061, USA alexey@cs.vt.edu.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Onufriev
mesh_terms: D003035:Cobalt / Q000378:metabolism; D059371:DNA, B-Form / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D012330:RNA, Double-Stranded / Q000737:chemistry* / Q000378:metabolism; D055672:Static Electricity
chemical_list: D059371:DNA, B-Form; D012330:RNA, Double-Stranded; C032300:hexaamminecobalt(II); D003035:Cobalt