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Title: Multi-shell model of ion-induced nucleic acid condensation

Journal Article · · Journal of Chemical Physics
DOI:https://doi.org/10.1063/1.4945382· OSTI ID:22660860
 [1];  [2];  [3];  [4];  [1]
  1. Department of Computer Science, Virginia Tech, Blacksburg, Virginia 24061 (United States)
  2. Department of Physics, Virginia Tech, Blacksburg, Virginia 24061 (United States)
  3. School of Applied and Engineering Physics, Cornell University, Ithaca, New York 14853-3501 (United States)
  4. Advanced Computing, Mathematics, and Data Division, Pacific Northwest National Laboratory, Richland, Washington 99352 (United States)

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 aggregation free 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 aggregation free 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 DNA condensation. 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 NA condensation lends support to proposed NA condensation picture based on the multivalent “ion binding shells.”.

OSTI ID:
22660860
Journal Information:
Journal of Chemical Physics, Vol. 144, Issue 15; Other Information: (c) 2016 AIP Publishing LLC; Country of input: International Atomic Energy Agency (IAEA); ISSN 0021-9606
Country of Publication:
United States
Language:
English

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Explicit ions/implicit water generalized Born model for nucleic acids journal May 2018
Counterion-Dependent Mechanisms of DNA Origami Nanostructure Stabilization Revealed by Atomistic Molecular Simulation journal September 2019

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