In my previous post I discussed some basic design concerns that arise with atomically precise structures, and focused on materials having crystalline order. However, the ability to make structures like these is now extremely limited. Because they can’t yet be built systematically from smaller building blocks, structures of this general are more likely to be discovered than designed, and the ability to make one doesn’t necessarily imply the ability to make similar ones with a few parameters adjusted.
Structural DNA nanotechnology is an orderly process
Structural DNA nanotechnology doesn’t produce crystals, but it does make systematic use of small building blocks, and can therefore make members of an enormously large combinatorial space of possible designs. Further, the orderly structure of DNA imposes discrete size and shape constraints somewhat like those of crystals.
Although the constraints on the size and shape of components are different from those encountered in designing steel parts, the structure of DNA strands and crossover junctions is simple and regular enough to enable designers to think about them in a systematic and productive way.
requires computational puzzle-solving
Designing proteins is very different, and more difficult. The advantages of proteins are a direct consequence of the diverse sizes, shapes, and chemical properties of the 20 different side chains of the standard amino acids. These enable proteins to have very different shapes and surface properties, as shown (for example) by the diversity of enzymes and antibody binding sites. Further, protein structures can have much greater mechanical stiffness than DNA, in part as a consequence of densely-packed interiors in which side chains fit together like puzzle pieces.
Side chains interact in irregular ways, though. Instead of the simplicity of a crystal lattice or the regularity of the Watson-Crick pairing and stacked bases in DNA, we find irregular molecular parts that must fit together, but don’t form in a regular or comprehensible pattern: The puzzle pieces fit together in a puzzling way. In the world of protein engineering, design depends on searching a combinatorial space of possible side-chain sequences and configurations, and this search process depends on modeling to evaluate the molecular interactions that determine the score of each option.
My starting point in thinking about nanotechnology was protein engineering, a problem that was misunderstood and regarded as too difficult to attempt. My first paper in the area (PNAS, 1981) argued that protein engineering could be accomplished, which it has, and based on ideas that grew out of that paper. Since protein engineering is a peculiar business, yet is central to some attractive near-term objectives in nanosystem engineering, the subject deserves its own post, which seems sure to grow into a series.
State-of-the-art protein engineering on your machine
If you’d like what amounts to hands-on experience with how protein chains fold, using an interactive, state-of-the-art model, have a look at FoldIt!, from the Baker Lab at UW. It’s serious science in the form of a game. If you have spare machine cycles to contribute to science, please take a look at Rosetta@home, another Baker Lab production.