Nature, 19 March 2009: Design and engineering of an O2 transport protein by Ronald Koder, JL Ross Anderson, Lee Solomon, Konda Reddy, Christopher Moser & P Leslie Dutton
Most protein design consists of tweaking an existing, natural structure, often using directed evolution with the occasional bit of deliberate peptide insertion so that it will bind to a specific molecule. Take the work of Angela Belcher's team at MIT, for example, where the coat protein was altered to include an amino acid known to bind to carbon nanotubes or to iron phosphate.
The idea of deliberate protein design suffered a serious blow when Professor Homme Helliga and researchers in his lab had to withdraw a couple of papers. Collaborators were unable to repeat Hellinga's results - instead of creating a structure from scratch that could act as a ribose binding protein, some of the wild-type protein wound up in the experiment and was responsible for all the desired activity.
One big problem is that proteins are complex structures. But much of that complexity comes from the way evolution works, with bits of genes getting copied, inserted, knocked out and mutated.
"This complexity frustrates biochemists seeking to understand structure and function and presents an extraordinary challenge to protein engineers who aim to reproduce or create new functions in proteins," argue the authors of the Nature paper.
If you design a protein from scratch, is it worth following the example of the natural world? "However common it may be in nature, we maintain that complexity is not an essential feature of protein as a material, nor is it an essential feature of catalysis, as shown by synthetic chemical systems," the authors reckon.
Eric Drexler of nanomachine fame, agrees: "...close adherence to natural models is often intellectually and technologically crippling."
The idea behind this paper is to use protein structures that are much simpler than those employed by nature, and more akin to regular catalysts.
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