THIS GRANT IS A CONTINUATION OF N00014-14-1-0609 Computer-Aided Engineering for Nucleic Acid-Based Nanotechnology
Abstract
Programmed self-assembly of nucleic acids offers the ability to manufacture materials at the sub-40 nanometer-scale for diverse applications in biomaterials science and nanotechnology. While scaffolded DNA origami is currently the most successful realization of this paradigm, recently the single-stranded tile approach has also demonstrated the powerful ability to program nanometer-scale features in extended crystals of DNA. Like macroscopic materials and structures, form follows function for DNA-based materials (i.e. the shape of a DNA nanostructure is based upon its intended function or purpose). Specifically, the 3D Angstrom-level shape of DNA-based nanostructures together with their mechanical properties play a central role in their emergent functional properties, which may include templates for metallic and silicon dioxide nanowires, casting containers for metallic nanoparticle fabrication, scaffolds for light-harvesting antennas and multi-enzyme cascades, as well as probes for biomembrane-related cellular processes. Conventional molecular modeling approaches for the determination of DNA nanostructure shape, such as Molecular Dynamics or Monte Carlo simulation, are inapplicable to structural DNA nanotechnology because of the high molecular weight and long time-scales that must be sampled to equilibrate these assemblies. The computational cost would just be too high. As an alternative, the Principal Investigator recently introduced a finite element based modeling approach called CanDo (Computer Aided eNgineering for DNA Origami). However, this model is limited to brick-like objects assembled on a honeycomb or square lattice using the principle of scaffolded DNA origami. In the proposed research, CanDo will be broadened by enabling the shape prediction of full off-lattice DNA nanostructures, including double- and single-crossovers to model extended single-stranded tile structures; 3-way and 5-way junctions; nicked and gapped B-form DNA; and extended crystalline DNA-based lattices consisting of arbitrary combinations of these elemental structural motifs. The development of CanDo relies critically on the atomistic simulation of elemental motifs that are used to inform the coarse-grained representation, which is validated extensively experimentally using atomic force microscopy, transmission electron microscopy, and cryo-electron microscopy data. Further, development of the coarse-grained shape prediction model CanDo serves to establish the fundamental principles that govern the determination of large-scale shape and flexibility of DNA-based nanostructures, which can then be subsequently leveraged by the broader nanotechnology community for the design of novel nanostructured biomaterials.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Sep 26, 2018
- Source ID
- N000141612181
Entities
People
- Mark Bathe
Organizations
- Massachusetts Institute of Technology
- Office of Naval Research
- United States Navy