title: Multi-shell model of ion-induced nucleic acid condensation.
abstract: We present a semi-quantitative model of condensation of short nucleic acid (NA) duplexes induced by trivalent cobalt(iii) hexammine (CoHex) ions. The model is based on partitioning of bound counterion distribution around single NA duplex into "external" and "internal" ion binding shells distinguished by the proximity to duplex helical axis. In the aggregated phase the shells overlap, which leads to significantly increased attraction of CoHex ions in these overlaps with the neighboring duplexes. The duplex aggregationfree energy is decomposed into attractive and repulsive components in such a way that they can be represented by simple analytical expressions with parameters derived from molecular dynamic simulations and numerical solutions of Poisson equation. The attractive term depends on the fractions of bound ions in the overlapping shells and affinity of CoHex to the "external" shell of nearly neutralized duplex. The repulsive components of the free energy are duplex configurational entropy loss upon the aggregation and the electrostatic repulsion of the duplexes that remains after neutralization by bound CoHex ions. The estimates of the aggregationfree energy are consistent with the experimental range of NA duplex condensation propensities, including the unusually poor condensation of RNA structures and subtle sequence effects upon DNAcondensation. The model predicts that, in contrast to DNA, RNA duplexes may condense into tighter packed aggregates with a higher degree of duplex neutralization. An appreciable CoHex mediated RNA-RNA attraction requires closer inter-duplex separation to engage CoHex ions (bound mostly in the "internal" shell of RNA) into short-range attractive interactions. The model also predicts that longer NA fragments will condense more readily than shorter ones. The ability of this model to explain experimentally observed trends in NAcondensation lends support to proposed NAcondensation picture based on the multivalent "ion binding shells."
authors.affiliation: Department of Computer Science, Virginia Tech, Blacksburg, Virginia 24061, USA.
authors.forename: Igor S
authors.initials: IS
authors.lastname: Tolokh
authors.affiliation: Department of Physics, Virginia Tech, Blacksburg, Virginia 24061, USA.
authors.forename: Aleksander V
authors.initials: AV
authors.lastname: Drozdetski
authors.affiliation: School of Applied and Engineering Physics, Cornell University, Ithaca, New York 14853-3501, USA.
authors.forename: Lois
authors.initials: L
authors.lastname: Pollack
authors.affiliation: Advanced Computing, Mathematics, and Data Division, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Baker
authors.affiliation: Department of Computer Science, Virginia Tech, Blacksburg, Virginia 24061, USA.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Onufriev
mesh_terms: D003035:Cobalt / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D012313:RNA / Q000737:chemistry*
chemical_list: C030862:cobalt ammonium complex; D003035:Cobalt; D012313:RNA; D004247:DNA