Probing the Mechanical Properties of DNA Nanostructures with Metadynamics.


Type
Article
Change log
Authors
Kaufhold, Will T 
Di Michele, Lorenzo  ORCID logo  https://orcid.org/0000-0002-1458-9747
Abstract

Molecular dynamics simulations are often used to provide feedback in the design workflow of DNA nanostructures. However, even with coarse-grained models, the convergence of distributions from unbiased simulation is slow, limiting applications to equilibrium structural properties. Given the increasing interest in dynamic, reconfigurable, and deformable devices, methods that enable efficient quantification of large ranges of motion, conformational transitions, and mechanical deformation are critically needed. Metadynamics is an automated biasing technique that enables the rapid acquisition of molecular conformational distributions by flattening free energy landscapes. Here we leveraged this approach to sample the free energy landscapes of DNA nanostructures whose unbiased dynamics are nonergodic, including bistable Holliday junctions and part of a bistable DNA origami structure. Taking a DNA origami-compliant joint as a case study, we further demonstrate that metadynamics can predict the mechanical response of a full DNA origami device to an applied force, showing good agreement with experiments. Our results exemplify the efficient computation of free energy landscapes and force response in DNA nanodevices, which could be applied for rapid feedback in iterative design workflows and generally facilitate the integration of simulation and experiments. Metadynamics will be particularly useful to guide the design of dynamic devices for nanorobotics, biosensing, or nanomanufacturing applications.

Description
Keywords
DNA nanotechnology, DNA origami, Metadynamics, Molecular dynamics, Molecular simulation, Nucleic Acid Conformation, Nanotechnology, Nanostructures, DNA, Molecular Dynamics Simulation
Journal Title
ACS Nano
Conference Name
Journal ISSN
1936-0851
1936-086X
Volume Title
16
Publisher
American Chemical Society (ACS)
Sponsorship
Engineering and Physical Sciences Research Council (EP/P020259/1)