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Blasting antibodies with lasers provides direct way of measuring their flexibilities

A group of scientists at The Scripps Research Institute (TSRI) and San Diego Supercomputer Center at the University of California at San Diego (UCSD) have used a powerful laser in combination with innovative quantum mechanical computations to measure the flexibility of mouse antibodies.

The new technique, described in an upcoming issue of the journal Proceedings of the National Academy of Sciences, is significant because protein flexibility is believed to play an important role in antibody-antigen recognition, one of the fundamental events in the human immune system.

"This is the first time anybody has ever gone into a protein and experimentally measured the frequency of protein vibrations in response to an applied force," says Floyd Romesberg, assistant professor in the Department of Chemistry at The Scripps Research Institute, who led the study.

"Our results show that the motions of the antibody-antigen complexes can range over four orders of magnitude, from tens of femtoseconds to hundreds of picoseconds," says co-author Kim K. Baldridge, Ph.D., director of Integrative Computational Sciences at the San Diego Supercomputer Center and an adjunct professor of Chemistry at UCSD. "This is evidence of a general mechanism of antigen-antibody interactions--which range from rigid to flexible," she adds.

Flexibility of Proteins

Protein flexibility is an important concept in biology because of its role in protein-protein and protein-ligand recognition. One of the longest running debates in molecular recognition is how proteins recognize and bind to other molecules--whether it resembles putting a key into a lock (the lock and key model) or catching a baseball in a catcher's mitt (the induced fit model).

There are lots of ideas about mechanisms of antigen recognition postulated in the literature, but what the debate comes down to is really a question of flexibility. How flexible are proteins?

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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
17-Dec-2002


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