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

We present a semi-quantitative model of condensation of short nucleic acid (NA) duplexes in- duced by tri-valent cobalt 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. The duplex aggregation free energy is de- composed into attraction and repulsion components represented by simple analytic expressions. The source of the short-range attraction between NA duplexes in the aggregated phase is the in- teraction of CoHex ions in the overlapping regions of the “external” shells with the oppositely charged duplexes. The attraction depends on CoHex binding affinity to the “external” shell of nearly neutralized duplex and the number of ions in the shell overlapping volume. For a given NA duplex sequence and structure, these parameters are estimated from molecular dynamics simula- tion. The attraction is opposed by the residual repulsion of nearly neutralized duplexes as well as duplex configurational entropy loss upon aggregation. 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 conden- sation. The modelmore » predicts that, in contrast to DNA, RNA duplexes may condense into tighter packed aggregates with a higher degree of duplex neutralization. The model also predicts that longer NA fragments will condense easier 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”.« less
Authors:
 [1] ;  [2] ;  [3] ; ORCiD logo [4] ;  [5]
  1. Department of Computer Science, Virginia Tech, Blacksburg, Virginia 24061, USA
  2. Department of Physics, Virginia Tech, Blacksburg, Virginia 24061, USA
  3. School of Applied and Engineering Physics, Cornell University, Ithaca, New York 14853-3501, USA
  4. Advanced Computing, Mathematics, and Data Division, Pacific Northwest National Laboratory, Richland, Washington 99352, USA; Division of Applied Mathematics, Brown University, Providence, Rhode Island 02912, USA
  5. Department of Computer Science, Virginia Tech, Blacksburg, Virginia 24061, USA; Department of Physics, Virginia Tech, Blacksburg, Virginia 24061, USA
Publication Date:
OSTI Identifier:
1253868
Report Number(s):
PNNL-SA-114165
Journal ID: ISSN 0021-9606; WN0219080
DOE Contract Number:
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Chemical Physics; Journal Volume: 144; Journal Issue: 15
Publisher:
American Institute of Physics (AIP)
Research Org:
Pacific Northwest National Laboratory (PNNL), Richland, WA (US)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
electrostatics; x-ray scattering; dna; molecular dynamics