The study, published in the Journal of Medicinal Chemistry, builds on prior work that captured the nanosecond-by-nanosecond movements of a protein called neuraminidase 1 (or N1), needed by the avian flu virus to spread infection to new cells. To help reveal the often-spasmodic motion of proteins, scientists work with molecular dynamics codes that simulate their movements as they obey the fundamental laws of physics. Such is the complexity of the mathematical calculations needed for these simulations that scientists often require the use of supercomputers. In this case, the researchers ran their data through a molecular dynamics program called NAMD - developed at the University of Illinois at Urbana-Champaign - on supercomputers at SDSC and the National Center for Supercomputing Applications in Illinois.
Some surprising details emerged as the scientists watched the protein gyrate and wiggle over time. In particular, one region dubbed a "hot pocket" appeared to be quite dynamic and flexible. Amaro said the topology of this region and the amino acids linking the pocket are significantly different from what the scientists previously observed in a static image of the protein's crystal structure.
"Crystal structures are very important," she said. "They give us a real picture of the protein. But it's just one picture."
Over the past decade or so, scientists have come to realize that the sometimes colorful structures gleaned from standard crystallography studies are limited. Instead of a still-life painting, proteins act more like a moving picture, constantly twitching and jiggling, making the goal of finding a specific inhibitor somewhat daunting. It's somewhat like a baseball pitcher attempting to throw strikes to a catcher who's doing handsprings behind home plate.
Molecular dynamics simulations already have proved their value for other dr
|Contact: Warren R. Froelich|
University of California - San Diego