Molecular Visualization in Nanotechnology Education, Research, and Outreach: Simulating Catalytic DNA Nanostars Using oxDNA

Through the NSF Future Manufacturing undergraduate research program at Pasadena City College (PCC), students utilize the tools of synthetic biology to build sustainable, DNA-based materials. The manipulation of DNA enables the construction of microscopic biochemical reactors through the formation of liquid-liquid phase-separated droplets, or DNA condensates. This research investigates the potential of DNA nanostars fused with G-tetraplexes, which can bind hemin, an iron-containing porphyrin co-factor, to form a DNAzyme capable of catalyzing peroxidation reactions within single condensate layers. The in vitro component of this research was enhanced by in silico coarse-grained molecular dynamics simulations, which generated 3D models of the DNA nanostars that allowed student researchers to visualize the behavior of the structures created in the laboratory. Leveraging this computational technique, student researchers developed educational resources and modular lessons to introduce these molecular simulations to a broad student audience at PCC. The simulation programs used, oxDNA and oxView, were instrumental in making this research accessible and engaging for diverse student groups. DNA nanostar simulations were integrated into the General, Organic, and Biochemistry curriculum at PCC, as well as during outreach events such as Girls Science Day, offering students insights into DNA nanostar dynamics and potential applications of DNA-based inventions. This paper details the use of simulation programs to recreate nucleic acid-based nanostructures, advancing the field of DNA nanotechnology. Molecular simulations helped the PCC research students develop experiments that demonstrate how enzymatic activity within DNA droplets can be achieved through G4 complexing. Simulating DNA nanostars with G4s was a profound educational exercise for students, as it taught them about the powerful synergy between in silico and in vitro experimentation. Students also learned about the limitations of modeling biomolecules using computational software, and our G4 simulation results may even inspire the integration of guanine-guanine interactions into the oxDNA program. These findings underscore the significant implications of in silico modeling and structural analysis in biochemical manufacturing and industrial applications, paving the way for further innovations in programmable biomolecular systems. By developing YouTube tutorials that teach students how to carry out nucleic acid simulations on any standard computer, the exploration of DNA dynamics and molecular programming is now widely accessible to both students and educators.