Researchers at Ohio State University are using the power of supercomputing to find the best molecular configuration to block proteins responsible for breast and prostate cancers. OSU Assistant Professor Chenglong Li and his graduate student Vandana Kumari are using the Ohio Supercomputer Center’s high-performance computing resources to search through thousands of possible molecular combinations that could block interleukin-6, which is often overproduced in individuals with cancer.
In 2002, a team of Japanese researchers found that a non-toxic molecule called madindoline A, or MDL-A, could be used to suppress the IL-6 signal. Following up on this research, Li is using a screening program and an OSC compute cluster to sift through more than 6,000 drug fragments to construct an MDL-A derivative that would dock with one of five “hot spots” on the IL-6 protein. So far, Li and his colleagues have identified two possible solutions by combining parts of the MDL-A molecule with sections of a benzyl or pyrazole molecule.
To define the interactions between IL-6 and two additional helper proteins, Li needed a powerful computational resource to run his simulations; he used molecular modeling software packages like AMBER and AutoDock. “Super-computing is needed at various stages for this drug design project [because] molecular dynamics simulations are required to pinpoint the feasible hot spots among the protein binding interfaces with ensuing free energy calculations,” Li says. “Massive numbers of fragment combinations need to be simulated and lead optimizations require detailed free energy simulations, so parallel runs at OSC Glenn cluster have been greatly facilitating the discovery process.”
Ultimately, Li hopes that this approach could change how research for both cancer treatment and prevention is done. “Regarding treatment, targeting the tumor microenvironment, and inhibiting tumor stem cell renewal might lead to a novel way to overcome breast and prostate cancer drug resistance and stop metastasis and recurrence,” he says. “As far as cancer prevention is concerned, breaking the link between chronic inflammation and cancer may offer a new strategy.” Read more…