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Top view of conotoxin LsIA binding to a receptor. Image from a in the journal Marine Drugs.

Sufferers of chronic pain know the debilitating consequences of the illness. Existing treatments for chronic pain tend to activate a wide range of receptors in the brain instead of just the few specific ones being targeted. Each receptor subtype has a different role, and off-target effects on the wrong receptor subtype can cause serious problems.

If we could find or create larger and more carefully shaped drug molecules, they would be able to selectively bind only to targeted receptors. Off-target activations of other receptors would be eliminated. To find suitable molecules, researchers have turned to an unlikely source: venom from marine cone snails. Conotoxins, the compounds found in cone snail venom, are a growing source of interest for novel pain relief treatments.

Dr Andrew Hung from RMIT University is conducting detailed molecular dynamics simulations on the National Computational Infrastructure’s Gadi supercomputer to learn how conotoxins interact with target receptors in the brain. Using a large number of Gadi nodes to simulate many possible toxins in combination with different receptor subtypes, the research team has been able to make predictions tested and validated by experimental collaborators.

 “Gadi allows us to simulate the movements of these complex molecular systems for long enough to get a more accurate idea of how a protein really moves,” says Dr Hung. “It’s like a Bruce Lee movie: if you only see the opening credits, Bruce Lee doesn’t seem to do much. But watch the whole movie, and his impressive range of movements become obvious.”

Modelling the protein and drug interactions for an extended period of time using powerful HPC systems is important. A protein’s movement is closely tied to its function, but the effects causing those movements might not be obvious at first. In some cases, a drug might only slightly alter a protein’s structure—and thus its movement—through a series of subtle steps that take some time to come about. The Gadi supercomputer allows researchers to model complex molecular interactions in exquisite detail.

This story was provided by a supporting partner of Science at the Shine Dome.