Howard Hughes Medical Institute (HHMI) scientists made the discovery while studying how one rare strain of HIV can evade a commonly prescribed class of drugs used to treat the virus that causes AIDS. The strain of HIV contained mutations that are often seen after failure of treatment with protease inhibitors, drugs that block the action of the enzyme protease and prevent the virus from making mature, infective copies of itself. When protease inhibitors fail -- as they often do with a fast-mutating virus like HIV -- new drug targets become vital.
"Recognizing these variations in conformation -- the three-dimensional arrangement of the amino acids that make up a protein -- is the first step in identifying a new drug target," said Alex Perryman, first author of the study published early online in the journal Biopolymers on February 28, 2006.
Perryman did the research when he was an HHMI predoctoral fellow in the lab of Andrew McCammon, an HHMI investigator in the Biomedical Sciences program at the University of California, San Diego. Perryman is now an Amgen postdoctoral fellow in the lab of Stephen Mayo, an HHMI investigator at the California Institute of Technology.
"We hope these simulations will motivate the researchers in pharmaceutical or biotechnology companies to pursue the design of a new kind of inhibitor," Perryman said. "We are trying to lead other scientists toward a completely novel approach to fighting HIV infections."
In contrast to the colorful but static images on the covers of scientific journals, actual proteins are constantly quivering from the t
Contact: Jennifer Donovan
Howard Hughes Medical Institute