DNA and RNA nanotechnology are rapidly developing fields that use DNA and RNA molecules as basic building blocks for constructing self-assembled nanoscale structures and devices. Promising applications include novel materials for diagnostics, drug delivery, nanophotonics, biophysical studies, and protein structural biology, as well as devices to perform molecular computation. Development of these structures is currently done with a trial-and-error approach, which is costly and time consuming because each new design has to be experimentally tested and gradually optimized until the desired structure is achieved. Computer simulations can provide insight into the assembly and function of these systems and greatly simplify and accelerate the design process, as well as guide understanding of the nanostructure function. However, computer simulations require molecular simulation expertise and high performance computing infrastructures that are not readily accessible to experimental groups. In this project, we will develop a new web server to provide users with online automatized tools that can be used to design, simulate, and analyze the properties of DNA and RNA nanostructures. The web server will also contain a repository of previously reported nanostructures so that researchers can easily access and use existing designs and adapt them for their use. We will also develop new models for hybrid DNA/RNA and protein-DNA/RNA nanostructures, thereby extending the ability of computational design and verification to larger and more complex nanostructures. This project will benefit the public by creating a highly efficient integrated platform to store, edit, design and computationally analyze nanostructures, thus providing a common resource to groups working in nanotechnology while simultaneously expanding access to these nanostructures to researchers in other fields. The net result will be to speed up and integrate the development of nanotechnology, simplify the design process, and facilitate the extension of biomolecular nanostructures to practical applications. The tools will also be impactful for teaching the simulation methods and for outreach activities, where students will be taught the principles of simulation and self-assembly by using the tools to design their own nanostructures.
Despite significant progress in the development of experimental methods that allow for assembly and characterization of the DNA and RNA nanostructures, the lack of easy-to-use software tools for design of nanostructures still remain a major bottleneck for wider adoption of the DNA and RNA nanotechnology in other related fields. Novel methods for structure design and verification are needed for the field to reach its full potential. Furthermore, the nascent field of hybrid DNA-protein and RNA-protein nanotechnology currently lacks efficient coarse-grained tools that would allow for the simulation. This proposal will consist of 1) Creation of a web-based platform for the interactive design of DNA/RNA nanostructures, along with a publicly accessible webserver for simulations and analysis of nucleic acid nanotechnology; 2) Creation of a public online repository of successfully assembled and verified DNA and RNA nanostructures from the field, where researchers will be able to share and edit published designs, allowing easy sharing and extensions of nanostructures; 3) Extension of our previously developed models of DNA and RNA to include coarse-grained representation of proteins and DNA-RNA hybrids, thus enabling the design of hybrid protein-DNA/RNA nanomaterials. The project will require development of new methods for nanostructure visualizations and analysis coupled with interactive high performance simulations on GPU cards, and parametrization of new models on new experimental data of hybrid nanostructures. The proposed research will have significant societal and educational impact. The user-friendly design tool will be easily incorporated into both the graduate and undergraduate curriculum. We will also incorporate the tools also into our outreach activities among high school students and teacher. The online design tool will be used for crowd-sourced science for web-based nanostructure design competitions.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
