Research objectives and content
Based on a new structural NMR parameter that complements the Nuclear Overhauser Effect and scalar coupling constants, angles between bonding vectors in proteins and oligonucleotides will be measured and the impact on structure elucidation and the dynamics of the biomacromolecules will be explored.
The new method relies on relaxation via cross-correlated dipolar couplings between the four nuclei that form the two internuclear vectors under consideration. The corresponding relaxation rates can be derived from the relative intensities of the components of a double quantum multiplet. These rates depend on the angle between the bond vectors, which can therefore be measured directly, without any need for empirical calibration.
New insights into slow segmental motion of the structure of
biomacromolecules, that is related to their function, is expected from these measurements The methodology will be applied to the
thrombin-inhibitor rhodniin, the calcium binding protein calmodulin as well as to a hairpin loop from the plasmid replication control system of E. coli.
Training content (objective, benefit and expected impact)
A new method to measure bond angles, which does not rely on coupling constants and empirical calibrations, will be further developed to obtain insight in the structure and dynamics of biomacromolecules. This parameter is expected to be of great help in obtaining a better accuracy of structures of pharmaceutically relevant molecules in solution. The project requires a sound theoretical and experimental training, from which I will greatly benefit, improving my skills and promoting my education in the NMR field My scientific experience in the development of NMR methods for protein structure determination will contribute to the project.