from the Cutting-the-gordian-knot dept.
Custom-engineered proteins have long been seen as one possible route to molecular nanotechnology. But the challenge of understanding how and why protein molecules assume the shapes they do to perform their structural and functional roles, has been an enduring problem in the field of protein engineering.
A press release describes work that apparently explains at least some aspects of protein structure by working from first principles. "We have discovered a simple explanation, based solely on principles of geometry, for the protein's preference for the helix as a major component of its overall structure," says Jayanth R. Banavar, professor of physics at Penn State and a member of the team of U.S. and Italian research physicists that made the discovery. The work was also reported in the 20 July 2000 issue of the journal Nature.
From the press release:
"We have discovered a simple explanation, based solely on principles of geometry, for the protein's preference for the helix as a major component of its overall structure," says Jayanth R. Banavar, professor of physics at Penn State and a member of the team of U.S. and Italian research physicists that made the discovery. The finding is expected to be useful in such wide-ranging research areas as structural genomics, pharmaceuticals, protein engineering, and materials science.
"We applied mathematical ideas about optimal shapes of strings with maximum 'thickness' to proteins, which are string-like in that they have an amino-acid backbone that curls and bends itself into a number of characteristic shapes, including the helix," Banavar says.
Like any tool, each protein's shape plays a large role in determining its function. Banavar and his colleagues asked in mathematical language what shape would lead to certain known properties of proteins. This approach is different from the intensive ongoing effort in biochemical research to understand what shape a protein is most likely to take based on each chemical bond that can form within its backbone's distinctive sequence of amino acids. "Many different amino-acid sequences fold into the same or similar structures, which suggests that the structure may be of more fundamental importance than the amino-acid sequences," Banavar says. "Our work yields a simple and logical way of looking at protein shapes independent of complex biochemical interactions."
"A fascinating question to think about is why proteins take on certain basic shapes in their folded states," says Amos Maritan, professor of physics at the International School for Advanced Studies in Italy (SISSA) and a member of the research team. As a simple example of this approach, the researchers asked a series of mathematical questions about the optimal working shape of proteins, including the maximum space around each amino acid in the proteins' folded form, or "native state," and their ability to form that compact shape rapidly. For each calculation, the answer turned out to be a spiraling helix.
