PhD. Project (Start October 2005)

This interdisciplinary project is with the supervisors Dr. Robert Deeth and Professor Greg Challis, both in the Department of Chemistry.

Sidereophores are peptide-like substances excreted by many bacteria to scavenge iron - an essential metabolite - from the surroundings (e.g soil, host) which are dilute in soluble iron. These small molecules bind to iron(III) with very high affinity, and one known as desferrioxamine is used to treat iron overdose in humans.

Modelling these iron-siderophore complexes are considerably difficult as the system is too large to produce meaningful ab initio quantum mechanical calculations so instead molecular modelling (MM) simulations are used. At the moment there are no conventional MM techniques that can handle transition metals as they can form up to 12 covalent bonds at varying lengths - extremely difficult to handle empirically.

Instead, Rob Deeth has developed a system which handles the transition metal with Ligand Field Theory of d-Orbitals, whilst leaving the atoms not in the vincinity subject to conventional forcefields, and has implement this into a popular MM/MD program called MOE to form DommiMOE.

Can we use DommiMOE to model the siderophores, which uses QM (quantum mechanical) calculations to tune an MM model of transition metal complexes - can we find a way to predict

1. The structure of the Fe - siderophore complex.
2. The binding energy or strength of the Fe - siderophore complex

If these two questions can be answered, this could have implications on novel siderophore design for antibiotics, or to help find the binding sites of the membrane proteins that adsorb these complexes.