Programmable
DNA Lattices: Design Synthesis and Applications
New York University
Subcontract (Nadrian C. Seeman,
Principal Investigator):
STATEMENT OF WORK
The group at NYU will perform the following tasks: It will design a variety of DNA motifs expected to form 3D lattices, both periodic and aperiodic. It will apply current software and that to be developed by the Winfree and Reif groups to optimize both the geometry and sequences of those DNA motifs. It will synthesize (or if appropriate purchase) and purify the strands corresponding to those designs and self-assemble them into the desired motifs. It will attempt to form crystalline lattices with the DNA motifs, using the self-assembly methods developed in previous studies. When crystals appear, they will be characterized by X-ray diffraction methods. Derivatized crystals will be prepared, and the structures solved when the resolution is high enough to warrant such studies. DNA motifs appropriate for 2D arrangements will be designed as in above. 2D DNA motifs will be used as the basis to organize heterospecies of matter. These will include nucleic acid molecules (e.g., knots), nanocrystals, and proteins. When resolution of 3D crystals warrants it, attempts will be made to produce ordered guests within the host lattices. Nucleic acid guests will be tethered within lattices, and diffraction experiments performed to establish the extent of their ordering. Nanocrystals will be tethered in the same fashion as nucleic acid guests. We will assay the success of 3D periodic assembly via diffraction experiments. We have produced several preliminary crystalline lattices, and we have obtained diffraction from three of them. In one case, the unit cell dimensions and space group appear to be as designed, although the resolution is not as good as we would like. The key milestone would be host-lattice crystals that diffract to better than 10 Å resolution, within one year, better than 5 Å within two years, and 2.5 Å or better within 3 years. This is a resolution adequate for crystallography. We may need to lower the symmetry of the system to increase resolution [e.g., designing 3 different molecules for a pseudo-trigonal system to replace one molecule forced to produced a 120˚ angle in a symmetric system], but we are prepared to do this in succeeding years. In parallel, we must learn to tie down macromolecular guests. We will prototype the system by tying down nucleic acids, such as tight knots we have built, because nucleic acids are easier for use in the system at this time. We should be able to demonstrate tying down nucleic acids in 2D within two years. Incorporating the PX-JX2 device into lattices will help us prototype tying down more globular species, such as knots and proteins. We expect to be able to tie down nanocrystals in 2D within three years.