Through analysis, Rensselaer researchers have revealed a surprisingly simple mechanism by which the protein fragment penetrates the cell membrane. Positively charged HIV peptides are drawn to negative charges, and when an HIV peptide cannot satisfy itself with the negative charges available on the surface of the cell membrane it is directly attached to, it reaches through the membrane to grab negatively charged groups in the molecules on the other side, opening a transient hole in the cell. This hole allows the flow of water and other material into the cell. Once all the peptides have been neutralized, the reaction stops and the hole closes, leaving behind a healthy, viable cell.
“What we saw in our computer calculations wasn’t at all what we expected to see when we began,” says Angel Garcia, co-lead author of the paper and senior constellation professor of biocomputation and bioinformatics. “The mechanism for entrance in the cell was clear in one simulation, but in some instances simulations show one result and you never see that result again. Then we started doing other simulations and it kept happening again and again.”
Garcia collaborated on this research, which was published in the Proceedings of the National Academy of Sciences, with postdoctoral researcher Henry Herce. For the paper, the researchers reported a dozen different simulations run through a high-powered cluster of computers. Garcia’s computer cluster is now running simulations on the use of antimicrobial proteins which will open a pore in the cell and keep it open, killing the cell. Garcia hopes to harness the power of Rensselaer’s Computational Center for Nanotechnology Innovations (CCNI). The CCNI will allow him to compile two years’ worth of data on his normal cluster in just 10 to 20 days.