Protein design revolution points toward advanced nanotechnology

Back in 1981 Eric Drexler proposed that the molecular machinery found in living cells demonstrated the feasibility of producing artificial molecular machinery, and that further, it would be easier to engineer proteins from scratch to fold in ways useful for engineering molecular machinery than to fully understand the scientific problem of how naturally evolved proteins fold to create biological molecular machinery. The past 28 years has seen some progress toward engineering proteins from scratch, but the validity of Drexler’s original proposal has now been decisively demonstrated by scientists at the University of Pennsylvania who used basic engineering principles derived from studying natural proteins to design from scratch a simple and small protein that performed the function of carrying oxygen that is performed by natural globin proteins without having the “exquisitely refined functional properties reflected in the globin fold”. This nanotech advance is described in a press release from the University of Pennsylvania, via AAAS EurekAlert “Proteins by Design: Penn Biochemists Create New Protein from Scratch“:

No doubt proteins are complex. Most are “large” and full of interdependent branches, pockets and bends in their final folded structure. This complexity frustrates biochemists and protein engineers seeking to understand protein structure and function in order to reproduce or create new uses for these natural molecules to fight diseases or for use in industry.

Using design and engineering principles learned from nature, a team of biochemists from the University of Pennsylvania School of Medicine have built — from scratch — a completely new type of protein. This protein can transport oxygen, akin to human neuroglobin, a molecule that carries oxygen in the brain and peripheral nervous system. Some day this approach could be used to make artificial blood for use on the battle field or by emergency-care professionals. Their findings appear in the most recent issue of Nature [abstract].

“This is quite a different way of making novel proteins than the rest of the world,” says senior author P. Leslie Dutton, PhD, Eldridge Reeves Johnson Professor of Biochemistry and Biophysics. “We’ve created an unusually simple and relatively small protein that has a function, which is to carry oxygen. No one else has ever done this before.”

“Our aim is to design new proteins from principles we discover studying natural proteins,” explains co-author Christopher C. Moser, PhD, Associate Director of the Johnson Foundation at Penn. “For example, we found that natural proteins are complex and fragile and when we make new proteins we want them to be simple and robust. That’s why we’re not re-engineering a natural protein, but making one from scratch.”

Currently, protein engineers take an existing biochemical scaffold from nature and tweak it a bit structurally to make it do something else. “This research demonstrates how we used a set of simple design principles, which challenge the kind of approaches that have been used to date in reproducing natural protein functions,” says Dutton.

The usefulness of this accomplishment is not the production of an artificial protein that binds oxygen as does neuroglobin, but rather that basic engineering principles were used to build a simple, robust protein that worked despite differing from the complexity of natural evolved proteins. Dr. Drexler emphasized and elaborated this point over at his Metamodern blog, which includes a nice comment by the senior author of the research publication, Dr. Leslie Dutton. (Credit: Science Daily and Metamodern)

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