There is a continued need to make the atomistic potentials, used to understand enzyme-ligand interaction, more reliable and predictive. Thus, force fields and scoring functions need to be more rigorously integrated with quantum mechanics because the latter governs the behaviour of all molecules. Our in-house methodology called FFLUX-REG is rooted in small molecules but has very recently been developed to tackle enzyme-ligand interaction from a fresh more rigorous perspective. The modern ideas behind FFLUX-REG and the current abundance of computer power unlock more reliable insight, at atomistic level, and closer to the underpinning quantum mechanics. This approach creates a clear and unified context in which to interpret ligand-receptor interaction, and in a computationally advanced way.
The computational development lab of the PI teams up with the lab of the CoI who have deep knowledge of fundamental enzymology. Amongst the case studies are how phosphoglycerate kinase operates in the maturation of nucleoside analogue therapeutics, such as the anti-Covid19 drug remdesivir, how fundamental mechanisms of protein regulation are elicited by certain ligands but not others, such as allomorphy in -phosphoglucomutase, and how allosteric ligands modulate enzyme activity, such as binding to the myristoyl site of cAMP-dependent protein kinase. Our approach will provide unprecedented details of the primary interactions that control these various phenomena, which will provide the basis from which to design and test novel ligands with improved therapeutic value.
http://www.qct.manchester.ac.uk
https://www.research.manchester.ac.uk/portal/j.waltho.html
Entry Requirements
Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.
Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible.
How To Apply
To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the BBSRC DTP website www.manchester.ac.uk/bbsrcdtpstudentships
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/
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