Computing Nonequilibrium Conformational Dynamics of Structured Nucleic Acid Assemblies

Synthetic 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...