An official website of the United States government
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.
more »
« less
OxDNA.org: a public webserver for coarse-grained simulations of DNA and RNA nanostructures
Abstract OxDNA and oxRNA are popular coarse-grained models used by the DNA/RNA nanotechnology community to prototype, analyze and rationalize designed DNA and RNA nanostructures. Here, we present oxDNA.org, a graphical web interface for running, visualizing and analyzing oxDNA and oxRNA molecular dynamics simulations on a GPU-enabled high performance computing server. OxDNA.org automatically generates simulation files, including a multi-step relaxation protocol for structures exported in non-physical states from DNA/RNA design tools. Once the simulation is complete, oxDNA.org provides an interactive visualization and analysis interface using the browser-based visualizer oxView to facilitate the understanding of simulation results for a user’s specific structure. This online tool significantly lowers the entry barrier of integrating simulations in the nanostructure design pipeline for users who are not experts in the technical aspects of molecular simulation. The webserver is freely available at oxdna.org.
more »
« less
- Award ID(s):
- 1931487
- PAR ID:
- 10282992
- Date Published:
- Journal Name:
- Nucleic Acids Research
- Volume:
- 49
- Issue:
- W1
- ISSN:
- 0305-1048
- Page Range / eLocation ID:
- W491 to W498
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
We present a tutorial on setting-up the oxDNA coarse-grained model for simulations of DNA and RNA nanotechnology. The model is a popular tool used both by theorists and experimentalists to simulate nucleic acid systems both in biology and nanotechnology settings. The tutorial is aimed at new users asking "Where should I start if I want to use oxDNA". We assume no prior background in using the model. This tutorial shows basic examples that can get a novice user started with the model, and points the prospective user towards additional reading and online resources depending on which aspect of the model they are interested in pursuing.more » « less
-
null (Ed.)The emerging field of hybrid DNA–protein nanotechnology brings with it the potential for many novel materials which combine the addressability of DNA nanotechnology with the versatility of protein interactions. However, the design and computational study of these hybrid structures is difficult due to the system sizes involved. To aid in the design and in silico analysis process, we introduce here a coarse-grained DNA/RNA–protein model that extends the oxDNA/oxRNA models of DNA/RNA with a coarse-grained model of proteins based on an anisotropic network model representation. Fully equipped with analysis scripts and visualization, our model aims to facilitate hybrid nanomaterial design towards eventual experimental realization, as well as enabling study of biological complexes. We further demonstrate its usage by simulating DNA–protein nanocage, DNA wrapped around histones, and a nascent RNA in polymerase.more » « less
-
Abstract This work seeks to remedy two deficiencies in the current nucleic acid nanotechnology software environment: the lack of both a fast and user-friendly visualization tool and a standard for structural analyses of simulated systems. We introduce here oxView, a web browser-based visualizer that can load structures with over 1 million nucleotides, create videos from simulation trajectories, and allow users to perform basic edits to DNA and RNA designs. We additionally introduce open-source software tools for extracting common structural parameters to characterize large DNA/RNA nanostructures simulated using the coarse-grained modeling tool, oxDNA, which has grown in popularity in recent years and is frequently used to prototype new nucleic acid nanostructural designs, model biophysics of DNA/RNA processes, and rationalize experimental results. The newly introduced software tools facilitate the computational characterization of DNA/RNA designs by providing multiple analysis scripts, including mean structures and structure flexibility characterization, hydrogen bond fraying, and interduplex angles. The output of these tools can be loaded into oxView, allowing users to interact with the simulated structure in a 3D graphical environment and modify the structures to achieve the required properties. We demonstrate these newly developed tools by applying them to design and analysis of a range of DNA/RNA nanostructures.more » « less
-
We introduce oxNA, a new model for the simulation of DNA–RNA hybrids that is based on two previously developed coarse-grained models—oxDNA and oxRNA. The model naturally reproduces the physical properties of hybrid duplexes, including their structure, persistence length, and force-extension characteristics. By parameterizing the DNA–RNA hydrogen bonding interaction, we fit the model’s thermodynamic properties to experimental data using both average-sequence and sequence-dependent parameters. To demonstrate the model’s applicability, we provide three examples of its use—calculating the free energy profiles of hybrid strand displacement reactions, studying the resolution of a short R-loop, and simulating RNA-scaffolded wireframe origami.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1093/nar/gkab324
