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Computing Nonequilibrium Conformational Dynamics of Structured Nucleic Acid Assemblies
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posted on 2016-01-12, 00:00 authored by Reza Sharifi Sedeh, Keyao Pan, Matthew Ralph Adendorff, Oskar Hallatschek, Klaus-Jürgen Bathe, Mark BatheSynthetic
nucleic acids can be programmed to form precise three-dimensional
structures on the nanometer-scale. These thermodynamically stable
complexes can serve as structural scaffolds to spatially organize
functional molecules including multiple enzymes, chromophores, and
force-sensing elements with internal dynamics that include substrate
reaction-diffusion, excitonic energy transfer, and force–displacement
response that often depend critically on both the local and global
conformational dynamics of the nucleic acid assembly. However, high
molecular weight assemblies exhibit long time-scale and large length-scale
motions that cannot easily be sampled using all-atom computational
procedures such as molecular dynamics. As an alternative, here we
present a computational framework to compute the overdamped conformational
dynamics of structured nucleic acid assemblies and apply it to a DNA-based
tweezer, a nine-layer DNA origami ring, and a pointer-shaped DNA origami
object, which consist of 204, 3,600, and over 7,000 basepairs, respectively.
The framework employs a mechanical finite element model for the DNA
nanostructure combined with an implicit solvent model to either simulate
the Brownian dynamics of the assembly or alternatively compute its
Brownian modes. Computational results are compared with an all-atom
molecular dynamics simulation of the DNA-based tweezer. Several hundred
microseconds of Brownian dynamics are simulated for the nine-layer
ring origami object to reveal its long time-scale conformational dynamics,
and the first ten Brownian modes of the pointer-shaped structure are
predicted.