About the Project
Agonism. The key question for receptor function is how the agonist ATP and its derivatives trigger the opening of the channel, and how the receptor transits back from the open, ATP-bound to the closed state via a desensitized state. In preliminary work we have characterised structural requirements for agonist action . Based on this we want to further investigate and characterise the transition between different states of the receptor using Markov State modelling of unbiased molecular dynamics simulations, and steered molecular dynamics simulations.
Allosteric antagonism. We recently characterised an allosteric binding site in the P2X7R by site directed mutagenesis and molecular modelling . This site was confirmed by X-ray structures of the panda P2X7R with allosteric antagonists bound, which allowed us to confirm the accuracy of our modelling approach. The project aims to characterise the energetics of P2X7R allosteric binding by taking advantage of recent progress in free energy perturbation calculations and the characterisation of the chemical inhibitor space with descriptors based on molecular dynamics. Establishing accurate free energy calculations and quantitative pharmacore descriptors for allosteric P2X7R inhibitors are extremely useful for lead optimization, for classification of known antagonists and filtering candidates from virtual screening.
UK/EU applicants only.
Applicants are required to hold/or expect to obtain a UK Bachelor Degree 2:1 or better in a relevant subject.
The University of Leicester English language requirements apply where applicable:https://le.ac.uk/study/research-degrees/entry-reqs/eng-lang-reqs/ielts-65
How to apply:
To apply for the PhD please refer to the guidelines and use the application link at https://le.ac.uk/study/research-degrees/funded-opportunities/bbsrc-mibtp
Please also submit your MIBTP notification form at https://warwick.ac.uk/fac/cross_fac/mibtp/pgstudy/phd_opportunities/application/
Project / Funding Enquiries: [Email Address Removed]
Application enquiries to [Email Address Removed]
UK/EU fees and stipend at UKRI rates. For 2020 this will be £15,285 pa
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