Supercomputer modeling opens the door for developing new methods of HIV treatment, scientists

In the middle of last week Nature published the results of a study that established that the naturally occurring compound inositol hexakisphosphate (IP6), involved in both assembly and maturation of HIV-1, could be the key to developing new methods of treating the virus.

The international group of researchers, led by specialists from Cornell University (USA), managed to use the capabilities of the most powerful supercomputers for system simulations of the key block in the protective capsid HIV-1, to trace in detail the interaction of the molecule of inositol hexakisphosphate (IP6), which assists both assembly and maturation HIV-1, with structural HIV proteins.

According to scientists, the molecule IP6 plays a key role in the development of the virus.

"We, in collaboration with other researchers, have discovered that HIV uses this small molecule to perform its function," said co-author Juan R. Perilla of the Department of Chemistry and Biochemistry at the University of Delaware.

"This small molecule acts on two different stages of the virus assembly," added Robert Dick, a PhD student at the Volker Vogt Laboratory.

Perilla was responsible for modeling the interaction of IP6 with structural proteins of HIV CA-CTD-SP1 on NAMD using the XSEDE, Extreme Science and Engineering Environment, funded by the National Science Foundation.

"XSEDE provides a unique structure that allows us to use unique computing resources that meet the needs of a particular scientific problem. In addition, the system allows us to develop new analysis tools", Perilla said.

The work included also modeling on the Anton2 system of the Pittsburgh supercomputer center. The latter allowed long-term simulations to test the stability of the "immature assembly" of HIV and IP6 capsids.

Through XSEDE, the Stampede2 system at the Texas Advanced Computing Center simulated NAMD phosphatases of inositol IP3, IP4 and IP5 and their interactions with HIV proteins CA-CTD-SP1.

"Stampede2 allowed us to establish that the molecular interactions between HIV proteins and this small molecule stabilize a certain part of the virus," said Juan Perilla.

Talking about the results of the work, the scientist noted that in the search for solutions to the most difficult problems, specialists are increasingly inclined to use ultra-modern technical devices. According to him, only with the help of a computational microscope can we trace the processes in dynamics today.

"Many experimental methods are just a snapshot. With the help of a computer microscope, you can see how everything is going in the dynamics, "Perilla said.

"The results of this study open the door for the development of new methods of treatment," the scientist believes.

One of the possible options involves the development of compounds similar to IP6, and their binding to the same areas of HIV, that is, blocking the functions of the molecule and preventing the maturation of the virus.

"A cell can create millions of virus particles, but if they do not pass the maturation process, they are safe," Dick explained.