CAREER: Design and modeling for modular bionanotechnology and citizen science

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NONTECHNICAL SUMMARYBionanotechnology is a field that uses designed molecules to construct devices and structures at nanoscale level, with promising applications for the development of novel materials, detection devices, as well as platforms for therapeutics or diagnostics. However, construction of such devices presents significant technical challenges. Computer modeling can provide useful insights into the design mechanisms of such systems. Computer-aided design software is often used in our macroscale world to design e.g. computer chips, cars, planes, etc. so that the device operation can be tested and optimized in simulation first. Construction at the nanoscale however presents multiple challenges. As opposed to our macroworld, nanostructures are typically realized by self-assembly, where individual components randomly diffuse until they meet and assemble into a target structure. To realize more complex structures that would self-assemble in high yields, there is a need for a new simulation framework that can efficiently and, at the same time, accurately represent the assembly and function of such nanostructures. This project will develop a new modeling framework that is capable of simulating self-assembled DNA nanostructures, which currently represent one of the most advanced branches of bionanotechnology. The research team will use this framework to optimize nanostructure assembly for high yield, and computationally design new types of reconfigurable nanostructures. Next, the team will extend the modeling platform to allow for the incorporation of other organic/inorganic molecules and materials, and use it to design a nanoswimmer that can move preferentially in one direction. Overall, this project will facilitate the creation of new nanodevices capable of performing complex tasks that would be difficult to realize experimentally without a sophisticated modeling platform, and bring the field closer to large-scale industrial applications. For the education component of the project, the research team will develop new learning opportunities for university students and the general public. The main effort will involve developing an online citizen science platform, where users can use the simulation platform to design and optimize structures themselves, allowing to crowd-source nanotechnology designs. TECHNICAL SUMMARY:Nucleic acid nanotechnology is one of the most advanced branches of bionanotechnology, with promising applications ranging from biotemplated manufacturing to diagnostics and therapeutics. However, the system sizes (thousands of nucleotides) and the timescales associated with their assembly and function (minutes to hours) make their assembly kinetics very challenging to model. There is hence a pressing need in the field for computational modeling tools that can incorporate additional molecules and materials into the DNA or RNA nanostructures, simulate far-from-equilibrium processes such as ATP-powered motors, and capture nanostructures’ assembly and function over long experimental timescales. To address this challenge, this project will develop a new family of coarse-grained models that can simulate large scale nanosystems, use them to study DNA and RNA nanostructure assembly kinetics, and optimize their designs to improve yields. The PI will use this framework to design new types of DNA and RNA nanostructures with controlled folding pathways that specifically select one possible stable conformation of the molecule, thus creating a reconfigurable biomaterial. Next, the research team will use the modeling platform to design an ATP-powered nanoswimmer that is capable of directional motion.The general framework developed in this project will allow modular design and harness different materials (both organic and inorganic) and functional molecular complexes for nanotechnology construction, thus bringing the field of nanotechnology closer to industry-scale applications and incorporating theoretical modeling into the bionanotechnology design pipeline.The PI’s education program will focus on training undergraduate and graduate students in interdisciplinary research skills required to tackle problems in bionanotechnology harnessing approaches from diverse fields and creating practical hands-on research opportunities as part of the teaching program. Furthermore, this project will develop a citizen science online platform. The platform will use a game-like interface where the players will solve real scientific problems of designing functional DNA nanostructures that will be tested using the developed computer models. It will enable crowd-sourcing the design of nanostructures and hence provide a platform to engage the general public in nanotechnology research.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.