A team of scientists from the University of Chicago Research Computing Center, the Texas Advanced Computing Center at the University of Texas at Austin, the San Diego Supercomputer Center at the University of San Diego, and the Department of Defense High Performance Computing Center in Vicksburg, Miss., are using some of the nation’s most powerful supercomputers to study influenza virus replication.

The primary treatment for influenza A is Amantadine. The drug is an organic compound that blocks proton flow through the M2 channel, one of the main targets for antiviral therapies. Unfortunately, the treatment is becoming less effective as a consequence of viral evolution. Mutations in the flu virus have changed the ability of Amantadine to bind to the M2 protein. Currently, there is a big push to identify more effective compounds for blocking influenza proteins to help guard against deadly pandemics.

To simulate the complex process of proton transfer through the M2 channel, the research team commandeered four high-performance computing systems: the Midway high-performance computing cluster at the University’s Research Computing Center, as well as resources from the Texas Advanced Computing Center at the University of Texas at Austin, the San Diego Supercomputer Center at the University of San Diego, and the Department of Defense High Performance Computing Center in Vicksburg, Miss.

The combined HPC power facilitated multiscale simulations with unprecedented detail. The results validate the link between mutations on the M2 protein and drug resistance, a connection that had been demonstrated in experiments, but up to now had not been described computationally. It’s a breakthrough that’s two decades in the making – as that’s how long scientists and drug designers have been striving to understand the intricacies of the M2 channel.

“Computer simulation, when done very well, with all the right physics, reveals a huge amount of information that you can’t get otherwise,” reports one of the lead researchers, Gregory Voth, the Haig P. Papazian Distinguished Service Professor in Chemistry. “In principle you could do these calculations with potential drug targets and see how they bind and if they are in fact effective.”

Deconstructing the flow of protons and the role of the M2 channel will enable scientists to predict the effectiveness of potential drug targets. The team is now gearing up to make the simulation run faster and to explain the effects of drug resistant mutations. They also plan to expand their study to other forms of influenza, like influenza B, which has a different M2 channel and is completely resistant to Amantadine.

A paper describing the research appears in the Proceedings of the National Academy of Sciences Online Early Edition for the week of June 16-20, 2014. It was written by Ruibin Liang, a graduate student in chemistry at UChicago, and three co-authors.