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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.