INTELLECTUAL MERIT: DNA has proved to be a successful biomaterial for the self-assembly of nanoscale structures because of its inherent programmability and predictable structural features. The proposed research will use predictable non-canonical base pairing motifs to: (1) design and assemble DNA crystals in three-dimensions, and (2) apply these crystals as molecular scaffolds. Previously identified non-canonical base pairing motifs will be used to design and assemble scalable three-dimensional DNA crystals. New self-assembling non-canonical DNA motifs will be identified through high-throughput crystallization screening of many short DNA oligonucleotide sequences. This will also address fundamental questions about the structural diversity of DNA. The second area of study will focus on the application of three-dimensional DNA crystals as molecular scaffolds for biological and non-biological molecules. This research will test methods for attaching and orienting protein guest molecules within the internal solvent spaces of DNA crystals. DNA crystals will also be used to align carbon nanotube arrays and to assemble high aspect ratio metallic nanowires within the framework of a self-assembling biomaterial.
BROADER IMPACTS: This proposal describes fundamental steps for establishing a three-dimensional DNA-based host/guest structure determination system for solving protein crystal structures and for organizing nanomaterials. Host/guest structure determination would simplify protein crystallization and decrease the resource burden associated with crystallization trials. Ultimately, this would lead to improved human health through providing structural clues related to disease. The ability to organize nanomaterials with a self-assembled, biocompatible framework will also provide significant advances to generating components for molecular electronic devices. The research component of this proposal focuses on exploiting the self-assembly properties of DNA for engineering crystals, and the self-assembly theme will be used to develop a hands-on workshop targeted to middle and high school students. The workshop will introduce the fundamentals of self-assembly, describe biological processes where self-assembly is observed, how self-assembly can and has been used in engineering, and emphasize the interdisciplinary nature of science and engineering. Additionally, the research and educational components of this proposal will be directly merged through a macromolecular crystallography-training program based on crystallizing short DNA oligonucleotides. This training program will be in important part of identifying new non-canonical base pairing motifs that can be used in DNA crystal design.
