AlphaFold 3 - Aided Design of DNA Motifs To Assemble into Triangles.

Self-assembly of biomolecules provides a powerful tool for a wide range of applications in nanomedicine, biosensing and imaging, vaccines, computation, nanophotonics, etc. The key is to rationally design building blocks and the intermolecule interactions. Along this line, structural DNA nanotechnology has rapidly developed by limiting DNA secondary structures to primarily well-established, B-form DNA duplexes, which can be readily and reliably predicted. As the field evolves, more sophisticated structural elements must be introduced. While increasing the structural complexity, they bring challenges to predicting DNA nanostructures. In the past, a brutal and tedious error-and-trial approach has often been used to solve this problem. Here, we report a case study of applying AlphaFold 3 to model the structural elements to facilitate DNA nanostructure design. This protocol is expected to be generally applicable and greatly facilitates the further development of structural DNA nanotechnology.