The quintessential application for designing DNA-based
DNA can be programmed to self-assemble into target nanostructures, however, determining the precise sequences that will perform this feat is a computational problem so challenging, it has been the primary roadblock to progress in the field — until now.
Using the extreme-scale capacity of Frontier, inSēquio employs Opportunistic Evolution (OE) to evolve sequences that will self-assemble into any specified design. Part CAD (computer assisted design) application and part grid-enabled optimizer, inSēquio has changed the way nano-engineers approach their work. It's another great example of how easy access to grid services can accelerate not just an application, but an entire field.
DNA Nanotechnology Overview
Although DNA is most commonly known in its double-helical form, single-stranded DNA (ssDNA) is a polymer that can be used to build nanoscale structures that automatically self-assemble. DNA's four bases — adenine (A), cytosine (C), guanine (G) and thymine (T) — bond in a complementary fashion (A ~ T and C ~ G), so that complementary strands of ssDNA will automatically bond to form the familiar double helix.
In 1983, Dr. Nadrian Seeman — the undisputed "father" of DNA nanotechnology — theorized that specifically designed DNA sequences would automatically weave themselves together into target structures by using DNA's complementary binding properties. Later he designed and produced via self-assembly so-called double crossover (DX) molecules and with that the field was born.
Determining sequences of bases that will self-assemble into a given structure, while simultaneously minimizing any "accidental pairings" between sequences that could derail the assembly process, is an enormous computational challenge. The possible permutations is astronomical for even modestly sized structures — there over 1 trillion possible sequences over a strand of 20 bases. Most nanostructures of interest contain thousands of bases, so the problem of determining optimal sequences practically requires grid-scale capacity.
The inSēquio Sequence Design Studio
inSēquio makes it possible to design arbitrary DNA nanostructures with a simple-to-use graphical editor (built using the Eclipse Graphical Editing Framework [GEF]). The inSēquio editor allows nano-engineers to lay out a nanostructure visually. Users can rotate and bend strands, define bindings between base pairs, and copy and paste sequences and structures between design documents. The editor supports the IOS file format for DNA structures, a standard XML schema that can be exchanged with other DNA modeling tools.
Optimizations are launched against a Frontier grid to determine the base sequences needed for self-assembly of the target structure. The optimization algorithm used by inSēquio called opportunistic evolution (OE); it is one of the many evolutionary algorithms available in Parabon's Origin™ Evolutionary SDK. By employing potentially thousands of computers on a Frontier grid, the inSēquio optimizer evolves potentially trillions of candidate sequences in search of the ideal sequences for assembly based on a set of user-supplied criteria. The optimizer is fully customizable and can be extended with additional constraints or models as understanding of the behavior of DNA nanotechnology improves.