WASHINGTON: A pair of theoretical physicists at Rensselaer Polytechnic Institute has searched out a possible pathway that an HIV peptide takes to enter healthy cells.
The discovery of the surprisingly simple mechanism describing how this protein fragment penetrates the cell membrane is a result of an analysis of two years of biocomputation and simulation.
The researchers believe that their finding may help scientists treat other human illnesses by exploiting the same molecules that make HIV so deadly proficient.
During their study, the researchers discovered that the positively charged HIV peptide is drawn to negatively charged groups inside the cell membrane.
When the HIV peptide cannot satisfy itself with the negative charges available on the cell membrane surface 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.
"What we saw in our computer calculations wasn't at all what we expected to see when we began," said Angel Garcia, co-lead author 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," he added.
When the peptides were neutralized during the experiments, said the researchers, the reaction stopped and the hole closed, leaving behind a healthy, viable cell.
For the paper, the researchers reported a dozen different simulations run through a high-powered cluster of computers, each of which required a long process of testing and validating results.
Garcia's computer cluster is currently running simulations on the use of antimicrobial proteins which will open a pore in the cell and keep it open, killing the cell. Antimicrobial proteins have promising direct applications for killing harmful cells in the body.
The findings have been published in the Proceedings of the National Academy of Sciences (PNAS).
The discovery of the surprisingly simple mechanism describing how this protein fragment penetrates the cell membrane is a result of an analysis of two years of biocomputation and simulation.
The researchers believe that their finding may help scientists treat other human illnesses by exploiting the same molecules that make HIV so deadly proficient.
During their study, the researchers discovered that the positively charged HIV peptide is drawn to negatively charged groups inside the cell membrane.
When the HIV peptide cannot satisfy itself with the negative charges available on the cell membrane surface 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.
"What we saw in our computer calculations wasn't at all what we expected to see when we began," said Angel Garcia, co-lead author 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," he added.
When the peptides were neutralized during the experiments, said the researchers, the reaction stopped and the hole closed, leaving behind a healthy, viable cell.
For the paper, the researchers reported a dozen different simulations run through a high-powered cluster of computers, each of which required a long process of testing and validating results.
Garcia's computer cluster is currently running simulations on the use of antimicrobial proteins which will open a pore in the cell and keep it open, killing the cell. Antimicrobial proteins have promising direct applications for killing harmful cells in the body.
The findings have been published in the Proceedings of the National Academy of Sciences (PNAS).
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