Diversifying DNA origami: Generative design tools rely on grammatical rules to find optimal shapes

As the name suggests, DNA origami is a fabrication technique in which researchers fold DNA strands to create two- and three-dimensional nanostructures of precise shapes. These highly programmable structures have the potential to transform drug delivery, diagnostic medicine, nanomaterial formation, and molecular computing, but scientists can conceptualize them just as easily as making paper origami. Designs are limited.

To overcome creative blocks, researchers at Carnegie Mellon University’s School of Mechanical Engineering have developed a generative design tool that can generate wireframe DNA origami nanostructures that are optimally driven according to designer-defined constraints. I did.

“Scientists can now generate hundreds of nanostructures to fit their specific needs in minutes,” said AJ Vetsurini, Ph.D. in mechanical engineering. candidate.

Shape grammar rules, used in product and architectural design, are planning tools that help generate new designs by manipulating shapes to fit defined rules. Because the composition of DNA is determined by a simple set of rules (A pairs with T, C pairs with G), applying shape grammar to DNA origami creates rules to guide the formation of DNA structures. was an easy choice for the research team.

A new computer-aided design tool introduced in Nucleic Acids Research relies on grammar rules to iterate the design before outputting an optimal solution. This generative design process, called shape annealing, was pioneered by mechanical engineering professor John Cagan.

“This tool allows people to manufacture structures that they wouldn’t necessarily come up with on their own, but now they can exist in the world with purpose,” he said. said.

Leveraging the team’s deep knowledge of DNA nanotechnology, we realized that the majority of existing designs barely explored the design space. First, the complexity of creating highly anisotropic DNA origami shapes often hinders the exploration of potentially breakthrough designs. Additionally, most DNA origami uses standardized, commercially available single-stranded DNA “scaffolds” that have a fixed size, so designs can be very limited in terms of available materials. It happens often.

“Designing nanostructures is extremely difficult because it requires carefully plotting thousands of nucleobases in a specific order,” explained Rebecca Taylor, associate professor of mechanical engineering.

“Successful designs that meet desired outcomes in terms of mechanics, geometry, and material usage are extremely difficult challenges without incorporating multi-objective optimization into the design process, which is why our newly released tools are so effective. It is extremely easy to use and will enable scientists at all levels to create diverse designs, potentially accelerating advances in biomedical and nanotechnology applications. ”

Additionally, the team fabricated and characterized multiple designs generated by this new tool and demonstrated that this new pipeline is fully compatible with existing approaches for converting 3D meshes into base-level representations of DNA origami. I was able to show that.