The amazing molecular maquettes.

The amazing molecular maquettes

Proteins, in a manner of speaking, act as the body's busy bees. Whereas DNNs genetic code lays out the architectural plans for making an organism, proteins carry out many of the building and operating functions. That is, they do the work.

Thus the ability to design and make proteins from scratch has great appeal for biochemists. Once they've decided what task they want done, chemists can - at least in theory - make a simple version of the molecule needed to do that task. This could make possible many creative applications, ranging from medical treatments to biological sensors.

In the March 31 NATURE, Dan E. Robertson, a chemist at the University of Pennsylvania in Philadelphia, and his colleagues describe a way to design and make a multiheine protein, one distinguished by its ability to transfer energy. Falling into the same category as myoglobin, hemoglobin, and certain enzymes, proteins like these can accept and reject electrons. Thus, they can move energy across cell membranes and do bona fide biological work. Photosynthesis and cell respiration, for example, require this type of electron travel.

Robertson's team reports fashioning a peptide - or chunk of a protein -with four helices. Hooked to that peptide are the four key heine groups - similar to those of red blood cells' oxygen-ferrying molecules - characterized by iron atoms embedded in them.

This molecule is an "essential intermediate" - or steppingstone - for synthesizing "molecular maquettes," the researchers declare. Like sculptors and architects who make tiny, preliminary models (maquettes) of big sculptures and buildings, these chemists make "stripped-down, functional versions" of biologically useful proteins, says P. Leslie Dutton, a chemist at the University of Pennsylvania and a study coauthor.

"The question we're asking is this," says Dutton, himself a weekend painter: "If you start with a complex, naturally occurring protein with, say, 100 amino acids, how could you make a simple version of that protein that would work the same way?"

The synthetic molecule would "dodge the excessive, irrelevant information" contained in a protein by "dumping its biological baggage," leading to a less complex version that does the same thing, Dutton says. "We just want its fundamental activity."

Calling this groups report a "feasibility study" for engineering a specific molecule, Dutton nevertheless sees potential for general protein design. "What we've brought to this area of research are principles for engineering protein electron transfer and the desire to construct something," he says.

"This approach is different from other ways of making proteins; Dutton adds. "We're hanging heme components on a protein frame, the way nature does. But this direction, I hope, will open the doors to some new and exciting [biochemical] games."