Quantum chemistry free energy methods for drug optimisation
This is an industrially funded 4-year PhD project, in collaboration with Boehringer Ingelheim (BI), a leading pharmaceutical company. It includes a one-year placement in Oxford, during which in-depth training will be provided in fundamental theory, software development, and computational chemistry simulations. This training will be delivered by academics from the Universities of Southampton, Bristol and Oxford via the Centre for Doctoral Training in Theory and Modelling in the Chemical Sciences. Successful completion of year one will lead to the award of an Oxford MSc, and progression to a 3-year PhD research project, which will be based in Southampton, and will include close collaboration with BI and visits to their research labs in Germany.
This project will offer unique exposure to both academic and industrial research environments and is ideally suited to applicants who wish to make an impact in problems of real industrial relevance.
The goal of this project is to overcome the force field limitations in biomolecular free energy calculations by employing large-scale ab initio calculations. To achieve this goal we will develop hybrid free energy methods which start with force fields to compute free energy differences between different ligands but then compute the free energy of mutation from the classical to the quantum description (free energies are thermodynamic state functions so such a transition is well-defined). This work will build on our previous experience in this area [1,2] and will use the ONETEP linear-scaling DFT program , which we develop in our group. Particular challenges in this project will be the development of free energy methods that have high configurational overlap between the classical and the quantum description and produce accurate ensembles of structures in both descriptions. Relevant to this project are also the development of quantum methods that provide the most accurate description of biomolecular interactions (such as new generations of DFT approaches) while reducing the computational demands, and the calibration of explicit and implicit models for the solvent. The project will involve development of new theory and code within ONETEP and in stand-alone free energy methods programs.
The new methods will be validated in actual protein-ligand targets of relevance to the pharmaceutical industry. The project is supported by Boehringer Ingelheim (BI) and will be co-supervised by researchers from BI and by Professor Chris-Kriton Skylaris, and will involve periods of work with the BI computational chemists in Germany.
Full funding of fees and stipend for 4 years. Applications are accepted from self-funded international applicants, but funding restricted to UK/EU applicants only.
 S. J. Fox, J. Dziedzic, T. Fox, C. S. Tautermann, and C.-K. Skylaris, Proteins 82 (2014) 3335.
 C. Sampson, T. Fox, C. S. Tautermann, C. J. Woods, and C.-K. Skylaris, J. Phys. Chem. B 119 (2015) 7030-7040.
 C.-K. Skylaris, P. D. Haynes, A. A. Mostofi and M. C. Payne, J. Chem. Phys. 122 (2005) 084119.
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FTE Category A staff submitted: 44.80
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