Pittsburgh Supercomputing Center

FOR IMMEDIATE RELEASE                         CONTACT:
July 2, 1999                                       Michael Schneider
                                                   Pittsburgh Supercomputing Center
                                                   (412) 268-4960

Getting a Thumb-Lock on AIDS

Simulations at Pittsburgh Supercomputing Center Show Joint-Like Motion in Key HIV Protein

PITTSBURGH -- A scientist at the Pittsburgh Supercomputing Center, in collaboration with a team of HIV researchers, simulated the structure and movement of reverse transcriptase (RT), an HIV enzyme targeted by AIDS drugs. The results -- reported in PROTEINS (May 15) -- show a large-scale motion in the "thumb" region of the enzyme, confirming and enlarging upon x-ray crystallographic observations of RT's structure.

RT transcribes HIV's single-strand RNA to form double-stranded DNA, making it possible for HIV to replicate itself inside the immune system. Many AIDS drugs, including AZT, work by interacting with RT to block reproduction of the virus.

Crystallographic studies have shown that the 3D structure of the RT region that interacts with RNA resembles a hand -- with palm, fingers and thumb. These studies also suggest that the thumb opens when RT transcribes RNA, making space for DNA to fit into the palm. Blocking this joint-like movement, it's believed, may be the key to designing more effective RT-inhibitor drugs.

The simulations verify that the thumb closes when DNA is absent, and they identify what parts of the protein are involved in this large-scale motion. The success of these simulations, furthermore, say the researchers, shows that computational simulations can be a valuable aid in evaluating the potential for success of new RT-inhibitor drugs.

At nearly 10,000 atoms, RT is one of the largest enzymes ever simulated by molecular dynamics, a computational method for precisely tracking the atom-by-atom movements of proteins and other biomolecules, providing information that goes beyond laboratory research. PSC scientist Marcela Madrid used the CRAY T3D and T3E at Pittsburgh to carry out the simulations. She collaborated with Eddy Arnold and Jianping Ding of Rutgers University and Alfredo Jacobo-Molina of the Monterrey Institute of Technology in Mexico. The National Center for Research Resources of the National Institutes of Health supported this work.

More information, including graphics, about this research is available at: http://www.psc.edu/science/madrid.html

The Pittsburgh Supercomputing Center is operated by Carnegie Mellon University in consultation with the University of Pittsburgh and with the assistance of Westinghouse Electric Company. It was established in 1986 and is supported by several federal agencies, the Commonwealth of Pennsylvania and private industry.

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Revised: July 2, 1999

URL: http://www.psc.edu/publicinfo/news/1999/hiv-simulation_07-02-1999.html