NSF POSE: Phase II: Open-source ecosystem for nucleic acid nanotechnology modeling

Arizona State University, Scottsdale AZ

Investigators

Abstract

The field of nucleic acid bionanotechnology aims to manufacture nanoscale-sized devices and structures, with applications ranging from creating new biomaterials to diagnostics and therapeutic devices. One of the key factors to help the nucleic acid nanotechnology field to unlock its full potential and realize more complex designs at the nanoscale is the need of sophisticated modeling tools available to experimental laboratories. Manufacturing of modern-day machinery, such as cars, planes, and processors, relies on computer design and simulation testing (such as flow of air around airplane) as an essential part of the design process, using computer-aided design software. The oxDNA ecosystems comprises simulation models and design tools aimed at computer-based testing and validation of nucleic acid nanostructures that can aid experimentalists in testing their structures as well as in designing complex behavior that would be otherwise impossible to achieve without efficient modeling tools. The oxDNA software has now reached a maturity, and this project transitions it toward an open-source ecosystem, where academic researchers as well as the biotechnology industry contribute towards its development and together identify new functionalities that need to be added to push the frontier of the complexity of devices that can be manufactured at nanoscale. Together, these efforts unlock development and realization of the next generation of bionanotechnology devices. The oxDNA software is a set of tools, coarse-grained models, and associated web-based services to model DNA and RNA nanodevices, as well as DNA/RNA-protein hybrid nanostructures. To efficiently model the system sizes and timescales associated with assembly and operation of these devices, it coarse-grains the representation of nucleic acids while retaining the main properties of the molecules that are relevant to the nanostructure operation. The associated ecosystem of tools helps design these nanostructures, provides webservers to run the simulations and libraries to evaluate the simulation results, and redesigns the nanostructures to perform desired function. All tools are developed under GNU Public License and are freely accessible along with their source code. This project deploys new simulation servers, improves the usability of the GUI to make the tools more accessible to a broader user community, creates a network of developers by organizing in-person as well as online training workshops, and establishes the oxDNA ecosystem as an online resource for crowd-sourcing real-world design challenges for practical applications of DNA and RNA nanotechnology. The ecosystem has the potential for transformative impact on the nucleic acid nanotechnology field and associated biotech industry by enabling researchers to perform a large fraction of design in silico to create novel complex architectures. 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.