Why Proteins Spiral

20, 2000

University Park, Pa. -- Why do proteins coil up into spirals? A new answer to this question, which could aid the effort to identify the genetically determined shapes and functions of human proteins, is published in the July 20 issue of the journal Nature.

"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 who published the article.

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.

Proteins are the product of genes and also the structural stuff of cells and tissues. 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."

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.

"The development of an easier way to reliably predict what shape a protein folds into from a knowledge of the sequence of its amino acids would lead to a renaissance in the field of human genomics and our work may help to advance this effort," says Banavar of Penn State. "We also would like to understand what the fundamental shapes are in nature and whether there is some really simple principle behind nature's selection of these shapes.

Members of the research team include Banavar, professor and head of the Department of Physics at Penn State; Amos Maritan, professor of physics; Cristian Micheletti, postdoctoral fellow; Antonio Trovato, graduate student at the International School for Advanced Studies (SISSA), the Italian National Institute for Materials Physics (INFM), and the Abdus Salam International Center for Theoretical Physics in Italy; and Flavio Seno, assistant professor of Physics at The University of Padova and at the Italian National Institute for Materials Physics (INFM).

This work was supported by the Italian National Institute for Materials Physics (INFM), the U. S. National Aeronautics and Space Administration (NASA), the North Atlantic Treaty Organizations (NATO), and the Donors of the Petroleum Research Fund administered by the American Chemical Society.

For more information, go to: http://www.science.psu.edu/alert/Banavar7-2000-2.htm

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CONTACTS:

Jayanth Banavar: 814-863-1089

Cristian Micheletti: 011-39-040-2240463,

Barbara K. Kennedy (PIO): 814-863-4682,