Philadelphia-- Researchers at the University of Pennsylvania School of Medicine are the first to observe and measure the internal motion inside proteins, or its dark energy. This research, appearing in the current issue of Nature has revealed how the internal motion of proteins affects their function and overturns the standard view of protein structure-function relationships, suggesting why rational drug design has been so difficult.
The situation is akin to the discussion in astrophysics in which theoreticians predict that there is dark matter, or energy, that no one has yet seen, says senior author A. Joshua Wand, PhD, Benjamin Rush Professor of Biochemistry. Biological theoreticians have been kicking around the idea that proteins have energy represented by internal motion, but no one can see it. We figured out how to see it and have begun to quantify the so-called dark energy of proteins.
Proteins are malleable in shape and internal structure, which enables them to twist and turn to bind with other proteins. The motions that we are looking at are very small, but very fast, on the time scale of billions of movements per second, explains Wand. Proteins just twitch and shake. The internal motion represents a type of energy called entropy.
Current models of protein structure and function used in research and drug design often do not account for their non-static nature. The traditional model is almost a composite of all the different conformations a protein could take says Wand.
The researchers measured a protein called calmodulin and its interactions with six other proteins when bound to a protein partner one at a time. These binding partners included proteins important in smooth muscle contraction and a variety of brain functions.
Using nuclear magnetic resonance spectroscopy, the investigators were able to look at the changes in the internal motion of calmodulin itself in each of the six different protein bind
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
19-Jul-2007