Supervisory Team: Prof. Marina Carravetta, Dr. Giuseppe Pileio and Prof. Ilya Kuprov
Some nasty peptides (conotoxins in carnivorous snails, neurotransmitter mimetics in snake venoms) contain uncommon conformers of the proline amino acid. This project is about controlling and measuring proline’s unusual dihedral angles, and improve nuclear magnetic resonance (NMR) methods to gather structural and dynamics information, using fluorinated prolines (FPro) as natural prolines' proxies.
Proline is cyclic, with distinctive dihedral angles that set it apart from other amino acids. With various degrees of 19F substitution, fluorination is expected to control its structural properties. In particular, fluorine is known for its large chemical shift anisotropy (CSA), and careful modelling by density functional theory explicitly including the different molecular conformations will be required. Modelling of FPro relaxation, using CSA that is dependent on conformation in slow exchange, hence outside the remit of Redfield theory, will be one of the key targets.
Theory and simulation will proceed hand in hand with experiments under a variety of conditions, to test theoretical models, justify the experimentally determined values to embrace conformational disorder as intrinsic part of the model. The study of relaxation properties as function of magnetic fields, temperature and solvent viscosity will facilitate this task. The experimental methods will be strengthened by quantum optimal control excitation of the FPro spin system, building on fluorine-edited selective transfer approach (FESTA) methods, with the objective to extend to Pro-containing small peptides and proteins, where peak overlap is a significant challenge due to the complexity and size of the spin systems.
Moreover, proline appears in interesting places of regular proteins: sharp turns, secondary structure junctions, and disordered regions. Further attention will be on FPro interactions with neighbouring residues, such as polyproline chains, as well as with aromatic amino acids, as π-interactions are structurally very important and may be revealed through their effect on the internal Hamiltonian and on the proline conformation and dynamics.
You must have a UK 2:1 honours degree or its international equivalent.
This project is fully funded by The Leverhulme Trust.
The studentship will cover UK tuition fees, including Horizon Europe fee waiver, and you'll receive a standard UKRI stipend (living allowance) per year for up to 4 years.
You need to:
Applications should include:
If you have a general question, email our doctoral college (feps-pgr-apply@soton.ac.uk).
For an initial conversation, email Professor Marina Carravetta (M.Carravetta@soton.ac.uk).
The School of Chemistry and Chemical Engineering is committed to promoting equality, diversity inclusivity as demonstrated by our Athena SWAN award. We welcome all applicants regardless of their gender, ethnicity, disability, sexual orientation or age, and will give full consideration to applicants seeking flexible working patterns and those who have taken a career break. The University has a generous maternity policy, onsite childcare facilities, and offers a range of benefits to help ensure employees’ well-being and work-life balance. The University of Southampton is committed to sustainability and has been awarded the Platinum EcoAward.