Multilevel modelling of the dynamics and mechansism of enzymes (RDF17/APP/CHRISTOV)

The present project will be focused on understanding enzyme dynamics, mechanisms and binding by applying multilevel computational methods in direct comparison to experimental studies. In addition, the conformational properties of newly purified enzymes will be explored based on structures, modelled by homology. The subjects of this study will be non-heme iron-containing enzymes such as histone and DNA demethylases which are important for biomedicine. This will be an exciting opportunity for a postgraduate student to achieve training in state-of-the-art computational modelling methods, respecting his/her own interests, attitudes and individual learning style. He/She will interact actively with the supervisory team and also with other scientists from the Department of Applied Sciences at Northumbria University. The student will learn how to apply Molecular Dynamics (MD) simulations to explore the conformational flexibility of the overall protein structure, the dynamics of the interactions between substrates, cofactors and active site residues (hydrogen bonds, electrostatic interactions and van der Waals contacts), and how they influence the reaction mechanism and binding. The next level of training will include understanding enzyme mechanisms by i) using quantum chemistry methods on a cluster formed from the most important amino acid side chains from the active site, the substrate and the cofactor; ii) using more sophisticated the Combined Quantum Mechanical and Molecular Mechanical Method (QM/MM) in order to explore the impact of the conformational dynamics, mutational effects and long-range electrostatic interactions on the enzyme mechanism.

Relevant alternative mechanisms will be explored. The calculated mechanisms and activation barriers will be correlated to the experimentally measured ones. The graduate student will interact also with our external experimental collaborators in the UK, EU and USA. The postgraduate student will achieve training in building structural models of proteins using homology modelling, in combination with molecular dynamics simulations for their further refining and validating the by combination of calculated and experimental Circular Dichroism spectra.

Eligibility and How to Apply
Please note eligibility requirement:
• Academic excellence of the proposed student i.e. 2:1 (or equivalent GPA from non-UK universities [preference for 1st class honours]); or a Masters (preference for Merit or above); or APEL evidence of substantial practitioner achievement.
• Appropriate IELTS score, if required (evidence required by 1 August 2017).

For further details of how to apply, entry requirements and the application form, see
https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/

Please ensure you quote the advert reference above on your application form.
Deadline for applications: 20 January 2017
Start Date: 2 October 2017

Northumbria University is an equal opportunities provider and in welcoming applications for studentships from all sectors of the community we strongly encourage applications from women and under-represented groups.