across the pharmaceutical industry.
During the project, you will use a range of AI and computational chemistry tools to undertake three main pieces of work.
- Assessing plausibility of novel structures of small molecules. The key challenge to be addressed by the QM methods is whether the molecules suggested by AI are chemically feasible. This requires an assessment of the strength of the bond types that are present in the molecule and classification to three types: unbound, tightly bound and weakly bound. Molecules of medicinal chemistry value should feature only tightly bound bonds. Unbound bonds will be identified by optimising a three-dimensional version of the structure using any QM method. Weakly bound bonds are more challenging and we will use quantum molecular dynamics. You will also consider the impact of water on molecular stability.
- Assessing poses from docking and co-folding software. This work package will be the most substantial part of the project and will see you immersed in the group’s activities exploiting the theoceptor method. You will generate docking poses of each molecule binding to their target protein using several traditional docking methods (e.g. autodock vina and GOLD) as well as deep-learning based method GNINA and diffusion-based generative docking approach DiffDock. The same task will also be undertaken with all available co-folding methods (e.g. Boltz-2 and Alphafold-3).
- Assessing output of protein folding software. One of the interesting possibilities that is frequently unexplored with protein folding tools such as Alphafold-2 is their ability to predict more than one reasonable conformation for a protein. Having identified the best methods for obtaining binding energies with docking, one of the applications that will be explored will be to systems such as GPCRs where multiple conformations can be biologically relevant. The challenge is labelling these alternative conformations according to their functional relevance. In this work package, you will apply the preferred methods identified in 2 to use the mode of action and binding strength of small molecule binders to identify those conformations best able to rationalise the known Structure-Activity Relationship.
You will work in a friendly group in the multi-disciplinary environment of the Division of Pharmacy and Optometry.
Entry Requirements
Applicants are expected to hold (or about to obtain) a minimum upper second-class undergraduate honours degree (or equivalent) in a chemical science (likely an MChem but other qualifications will be considered). Research experience in computational chemistry is desirable.
International applicants (including EU nationals) should ensure that they meet the academic eligibility criteria for the programme. Applicants who are offered a place will also need to meet the University's English language requirements before commencing their studies. Further information can be found on the University's English Language Requirements page.
Application Guidance
Candidates must contact the primary supervisor before applying to discuss their interest in the project and assess their suitability.
Apply directly via this link: https://tinyurl.com/mt2xfsvp or on the online application portal, select EPSRC DTP PhD as the programme of study.
You may apply for up to two projects within this scheme. If you wish to apply for two projects, you must submit a separate online application for each project, listing the relevant project title and main supervisor in each application.
Please ensure that your application includes all required supporting documents:
- Curriculum Vitae (CV)
- Supporting Statement
- Academic Certificates and Transcripts
Incomplete or late applications will not be considered. Further details are available on our website: EPSRC Doctoral Training Partnership | Biology, Medicine and Health | The University of Manchester
Equality, diversity and inclusion are central to the University’s activities. The full statement can be found here: https://www.bmh.manchester.ac.uk/study/research/getting-
Funding Notes
The EPSRC studentships provide full funding for tuition fees and a stipend at the Research Councils UK (UKRI) rate for 3.5 years starting in September 2027. Please note, candidates will need to cover the cost of relocation and any associated costs (e.g. visa, health surcharges).
