Structure and dynamics of multiple cationic vectors-siRNA complexation by all-atomic molecular dynamics simulations

Defang Ouyang, Hong Zhang, Harendra S. Parekh, Sean C. Smith

Research output: Contribution to journalArticle

Abstract

Understanding the molecular mechanism of gene condensation is a key component to rationalizing gene delivery phenomena, including functional properties such as the stability of the gene-vector complex and the intracellular release of the gene. In this work, we adopt an atomistic molecular dynamics simulation approach to study the complexation of short strand duplex RNA with four cationic carrier systems of varying charge and surface topology at different charge ratios. At lower charge ratios, polymers bind quite effectively to siRNA, while at high charge ratios, the complexes are saturated and there are free polymers that are unable to associate with RNA. We also observed reduced fluctuations in RNA structures when complexed with multiple polymers in solution as compared to both free siRNA in water and the single polymer complexes. These novel simulations provide a much better understanding of key mechanistic aspects of gene-polycation complexation and thereby advance progress toward rational design of nonviral gene delivery systems.
Original languageEnglish
Pages (from-to)9231-9237
Number of pages7
JournalJournal of Physical Chemistry: Part B
Volume114
Issue number28
DOIs
Publication statusPublished - 22 Jul 2010

Fingerprint

Complexation
genes
Small Interfering RNA
Molecular dynamics
Genes
molecular dynamics
Computer simulation
Polymers
RNA
simulation
polymers
delivery
wireless communication
strands
Condensation
topology
condensation
Topology
Water
water

Keywords

  • cations
  • gene transfer techniques
  • molecular dynamics simulations
  • polymers
  • small interfering RNA

Cite this

Ouyang, Defang ; Zhang, Hong ; Parekh, Harendra S. ; Smith, Sean C. / Structure and dynamics of multiple cationic vectors-siRNA complexation by all-atomic molecular dynamics simulations. In: Journal of Physical Chemistry: Part B. 2010 ; Vol. 114, No. 28. pp. 9231-9237.
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Structure and dynamics of multiple cationic vectors-siRNA complexation by all-atomic molecular dynamics simulations. / Ouyang, Defang; Zhang, Hong; Parekh, Harendra S.; Smith, Sean C.

In: Journal of Physical Chemistry: Part B, Vol. 114, No. 28, 22.07.2010, p. 9231-9237.

Research output: Contribution to journalArticle

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