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Title: Systematic coarse-grained modeling of complexation between small interfering RNA and polycations

All-atom molecular dynamics simulations can provide insight into the properties of polymeric gene-delivery carriers by elucidating their interactions and detailed binding patterns with nucleic acids. However, to explore nanoparticle formation through complexation of these polymers and nucleic acids and study their behavior at experimentally relevant time and length scales, a reliable coarse-grained model is needed. Here, we systematically develop such a model for the complexation of small interfering RNA (siRNA) and grafted polyethyleneimine copolymers, a promising candidate for siRNA delivery. We compare the predictions of this model with all-atom simulations and demonstrate that it is capable of reproducing detailed binding patterns, charge characteristics, and water release kinetics. Since the coarse-grained model accelerates the simulations by one to two orders of magnitude, it will make it possible to quantitatively investigate nanoparticle formation involving multiple siRNA molecules and cationic copolymers.
Authors:
 [1] ;  [1] ;  [2] ;  [2] ;  [2]
  1. Graduate Program in Applied Physics, Northwestern University, Evanston, Illinois 60208 (United States)
  2. (United States)
Publication Date:
OSTI Identifier:
22493384
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Chemical Physics; Journal Volume: 143; Journal Issue: 24; Other Information: (c) 2015 AIP Publishing LLC; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; ATOMS; COMPARATIVE EVALUATIONS; COMPUTERIZED SIMULATION; COPOLYMERS; GENES; GRAFTS; KINETICS; MOLECULAR DYNAMICS METHOD; MOLECULES; NANOPARTICLES; RNA; WATER