Researchers at North Carolina State University have harnessed the Jaguar supercomputer at Oak Ridge National Laboratory to examine the a possible link between protein misfolding and Parkinson’s disease.
The team behind the research initially pointed to copper as a primary ingredient responsible for the misfolding of a protein called alpha-synuclein. The researchers believe that certain metals, including copper, can create fibrillar plaques that are known to be present Parkinson’s patients, but until recently they have not been able to ascertain how the copper was binding to the protein.
As Frisco Rose, a Ph.D. candidate in physics and lead investigator behind the project stated, the problem can best be described by harkening back to the image of a school playground. In a release today he told readers to imagine a large swing set with a number of kids swinging and holding hands—an image that is parallel to the protein itself. He says that “copper is the kid who wants a swing…there are a number of ways that copper could grab a swing or bind to the protein, and each of those ways would affect all the other kids on the swing set differently.” In short, they want to find that binding process or, along with his metaphor, the unique way the “kid” decides to overtake a swing.
The team set to work developing a series of simulations that would attempt to look for the most likely binding scenario by looking at the interactions of many thousands of atoms and the dynamics of the possible misfolding. This required hundreds of thousands CPU-hour runs and required a new processing method due to the size of the required calculations.
According to the team, only Jaguar would have been able to tackle the problem, even with the refined computational methods. Their decision to make use of the supercomputer yielded answers to their questions—and definitive concepts that point to specific binding configurations that can lead to misfolding. These findings, which will be published this week in Nature Scientific Reports, could lead to innovative therapeutic methodologies for understanding and treating Parkinson’s disease.