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Characterization of the molecular interactions of venom peptides with model cell membranes

Research Team: Carlo Marinotti, Dr. Evelyne Deplazes, Prof. Ricardo Mancera
CIC Specialist: Shiv Meka

Spider venoms are a rich and yet mostly unexplored source of bioactive molecules. It is well known that spiders incapacitate their prey using a complex mix of neurotoxins, some of which has been found to be promising pharmacological leads due to their ability to inhibit pain response signals in humans. The mechanism of action of these so-called Inhibitor Cystein Knot peptides (ICK) is still unclear, but it has been shown experimentally that for some of them the membrane binding affinity correlates with their inhibitory activity. Experimental assays used to characterise the activity of these peptides tend to be expensive and time-consuming due to the non-trivial method of production of these peptides. The group’s work is aimed at the development of a computational protocol capable of predicting the affinity of some of these ICK with model cell membranes. For this purpose a computer simulation approach is needed to characterise the multiple possible interactions of these peptides with cell membranes. In collaboration with the CIC we are developing new computational methods capable of enhancing the exploration of the configurational space of membrane-ICK interactions. This approach will not only save a lot of unnecessary expense in the discovery phase of peptide-based drugs, but also have save large amounts of time by increasing the number of compounds that can be simultaneously studied.

This work was supported by resources provided by the Pawsey Supercomputing Centre with funding from the Australian Government and the Government of Western Australia.