Role of structural dynamics in interactions of peptides and proteins

For the understanding cellular systems it is necessary to reveal, at the atomic level, the structure activity relationship of polypeptides and proteins. The synchronized, specific and efficient interaction patterns of the above mentioned macromolecules secure most critical bioactivities such as signaling, energy transfer, or cell division. The present proposal aims to enhance the well known Structure Activity Relationship (SAR) paradigm with dynamics (Dynamics-Structure-Activity Relationships, or DSAR), where beside 3D-structural properties, the internal dynamical parameters of the interacting partner polypeptides and proteins, as well as their complexes is revealed (Gáspári & Perczel, ANNUAL REPORTS IN NMR SPECTROSCOPY, 2010, 71). The recently installed (2010) high-field NMR spectrometer (Bruker 700) at ELTE together with our expertise and existing cooperation network enable us to successfully accomplish such a task. The present proposal envisages the study of about a dozen interacting polypeptides and protein modules. Important systems, such as the Exendin 4/GLP1 related to the cure of type II diabetes mellitus, or self-aggregating peptides associated with Alzheimer's disease will be studied. The present research envisaged is basic research, although most of the macromolecular systems studied are related to key biochemical events or to drug development.