Biophysicist targets protein with supercomputer

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Chenglong Li, an assistant professor of medicinal chemistry and pharmacognosy at The Ohio State University (OSU), USA, is using a cluster at the Ohio Supercomputer Center (OSC) to develop a drug that will block the small protein molecule Interleukin-6 (IL-6). The body normally produces this immune-response messenger to combat infections, burns, traumatic injuries, etc. Scientists have found, however, that in people who have cancer, the body fails to turn off the response and overproduces IL-6.

Last year, Li partnered with an organic chemist and a cancer biologist at OSU’s James Cancer Hospital to investigate this further, using an OSC supercomputer to construct malleable, three-dimensional colour simulations of the protein complex. ‘We proposed using computational intelligence to re-engineer a new set of compounds that not only preserve the original properties, but also would be more potent and efficient,’ said Li. ‘Our initial feasibility study pointed to compounds with a high potential to be developed into a non-toxic, orally available drug.’

Li accessed 64 nodes of OSC’s Glenn IBM 1350 Opteron cluster to simulate IL-6 and the two additional helper proteins needed to convey the signal: the receptor IL-6R and the common signal-transducing receptor GP130. Two full sets of the three proteins combine to form a six-sided molecular machine, or ‘hexamer’, that transmits the signals that will, in time, cause cellular inflammation and, potentially, cancer.

The AMBER (Assisted Model Building with Energy Refinement) and AutoDock molecular modelling simulation software packages were deployed to help define the interactions between those proteins and the strength of their binding at five ‘hot spots’ found in each half of the IL-6/IL-6R/GP130 hexamer.