Essex Research Group

Computational Simulation of Biomolecular Systems

Charlie Holdship

My project focusses on conotoxins – naturally occurring neurotoxins made by cone snails and used to incapacitate prey. Specifically we are interested in 5 members of the α-conotoxin family which are highly selective antagonists of nicotinic acetylcholine receptors (nAChRs). In order to begin developing potential anti-toxins to combat these conopeptides, their structures in physiological conditions need to be investigated. This will be done using molecular dynamics simulations with sampling being enhanced by using the replica exchange method REST2.

Each of the conformations generated by these simulations will be used to calculate NMR properties of the compounds in order to validate the structures against published values. The results of these simulations will then be docked to adult nAChR in order to determine the binding geometries of the conotoxins. These will be compared and validated against the known binding poses of conotoxins to AChBP.