If you have an interest in working in the group, please get in touch by emailing Prof. Jonathan Essex at J.W.Essex@soton.ac.uk.
The search for first-in-class small molecule drugs is risky and expensive. The discovery of high quality and tractable chemical starting points (the hits) is an important milestone in addressing hard targets. Reliable in in-silico predictions (wihtout wet-lab work) with the likelihood to find and validate these quality hits experimentally, would be a game-changing tool. This project looks to combine and optimise two existing methods (SWISH and GCNCMC) to improve the quality of in-silico predictions for high-quality hits. This project is run in collaboration with Exscientia.
Binding free energy calculations are a widely used technique in the pharamceutical industry to identify potential drug candidates however they are not always successful. In cases where the calculated free energies are inaccurate, the errors may be ascribed to either inadequate sampling or a force field which does not represent the molecular interactions in the system. This project addresses the sampling problem and is run in collaboration with AstraZeneca and GSK to further validate and optimise the recently developed Fully Adaptive Simulated Tempering (FAST) procedure.
The aim of this project is to develop and apply the Sequential Monte Carlo (SMC) method in the context of biomolecular simulations. There is a long-standing interest in molecular simulation to develop enhanced sampling algorithms to address the known limitations of conventional molecular dynamics. SMC has been used in a number of fields, but has received little attention in biomolecular simulation. In this project, you will develop and apply the molecular-SMC approach to two main classes of problem in biomolecular modelling – to protein-ligand docking, and to binding free energy calculations.
Small angle X-ray scattering (SAXS) provides structural information in the solution phase at room temperature, but is limited in terms of resolution. In this multidisciplinary project, you will work in close collaboration with scientists at the Diamond Light Source (DLS) to develop theoretical methods and software to combine atomistic molecular simulations with SAXS data, to extend the structural information from SAXS experiments to higher resolutions.
The Antibody and Vaccine Group based in the newly opened Centre for Cancer Immunology in Southampton alongside colleagues at the Institute for Life Sciences in Macromolecular Crystallography and Computer simulation of Biomolecular Systems Group, are seeking to employ a Postdoctoral Research Fellow to help develop next generation antibody therapeutics.