Crucial step in AIDS virus maturation simulated for first time
Using computational techniques, researchers have shown how a protein responsible for the maturation of the virus releases itself to initiate infection
Barcelona, 04 December 2012 - Bioinformaticians at IMIM (Hospital del Mar Medical Research Institute)
and UPF (Pompeu Fabra University) have used molecular simulation techniques to explain a specific step in the maturation of the HIV
virions, i.e., how newly formed inert virus particles become infectious, which is essential in understanding how the virus
replicates. These results, which have been published in the latest edition of PNAS, could be crucial to the design of
HIV virions mature and become infectious as a result of the action of a protein called HIV protease. This protein acts
like a pair of scissors, cutting the long chain of connected proteins that form HIV into individual proteins that will form the
infectious structure of new virions. According to the researchers of the IMIM-UPF computational biophysics group, "One of the
most intriguing aspects of the whole HIV maturation process is how free HIV protease, i.e. the 'scissors protein,' appears
for the first time, since it is also initially part of the long poly-protein chains that make up new HIV virions."
Using ACEMD a software for molecular simulations and a technology known as GPUGRID.net, Gianni
De Fabritiis' group has demonstrated that the first "scissors proteins" can cut themselves out from within
the middle of these poly-protein chains. They do this by binding one of their connected ends
(the N-terminus) to their own active site and then cutting the chemical bond that connects
them to the rest of the chain. This is the initial step of the whole HIV maturation
process. If the HIV protease can be stopped during the maturation process, it will
prevent viral particles, or virions, from reaching maturity and, therefore, from becoming infectious.
This work was performed using GPUGRID.net, a voluntary distributed computing platform that harnesses the processing
power of thousands of NVIDIA GPU accelerators from household computers made available by the public for research
purposes. It's akin to accessing a virtual supercomputer. One of the benefits of GPU acceleration is that it
provides computing power that is around 10 times higher than that generated by computers based on CPUs
alone. It reduces research costs accordingly by providing a level computational power that previously
was only available on dedicated, multi-million dollar supercomputers.
Researchers use this computing power to process large numbers of data and generate highly complex molecular
simulations. In this specific case, thousands of computer simulations have been carried out, each for
hundreds of nanoseconds (billionths of a second) for a total of almost a millisecond.
According to researchers, this discovery in the HIV maturation process provides an alternative approach in the
design of future pharmaceutical products based on the use of these new molecular mechanisms. For now, this work
provides a greater understanding of a crucial step in the life cycle of HIV, a virus that directly attacks
and weakens the human immune system, making it vulnerable to a wide range of infections, and which
affects millions of people around the world.
Reference:"Kinetic characterization of the critical step in HIV-1 protease maturation". S Kashif Sadiq, Frank Noe and Gianni De Fabritiis. PNAS. DOI:10.1073/pnas.1210983109. www.pnas.org
IMIM (Hospital del Mar Medical Research Institute)
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