PhD Studentship: Biological Insights from the Analysis of Protein Conformational Variability

Primary Supervisor – Prof. Steven Hayward

Proteins are very flexible molecules, changing their shape or conformation to function. In the past, this dynamic aspect of protein function has been difficult to resolve. However, recent advances in cryo-genic electron microscopy (cryo-EM), time-resolved diffraction methods and AI-based prediction methods mean that individual conformational states along functional pathways can also be determined or predicted. Dynamics bridges the link between protein structure and protein function and understanding its role will inevitably lead to major technological advances in drug design and biotechnology. For example, in drug design, where it is known that the binding of a drug molecule to a protein target results in a conformational change in the protein, the design of a new drug molecule often relies on a single protein structure. 

In this project we will develop bioinformatics-based methods for analysing the large number of conformational ensembles that are now available from the Protein Data Bank (PDB) in order to make the link between structure and function by characterising dynamical behaviour. The project will be concerned primarily with domain motions within proteins, particularly within those proteins constructed from multiple subunits which are increasingly being deposited in the PDB as a result of the advances in cryo-EM.  

References 

Hayward, S. (2023). A retrospective on the development of methods for the analysis of protein conformational ensembles. The Protein Journal, 42(3), 181-191. https://doi.org/10.1007/s10930-023-10113-9. 

Funding Details

Additional Funding Information

This PhD project is in a competition for a Faculty of Science funded studentship. Funding is available to UK applicants and comprises ‘home’ tuition fees and an annual stipend of £19,237 (for a maximum 3 years)

Closing Date: 27 November 2024 (at 11.59 pm) 

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