Final Report Summary - HIDDENTIMENMR (NMR detected nanosecond to microsecond dynamics for biomolecular recognition dynamics)
The main function of proteins is to work as enzymes and components of complexes in signal transduction as well as more or less flexible scaffolds. For all these functions, the structure of the protein has to change. We studied whether these conformational changes are intrinsic properties of the proteins or whether they are induced by the substrates or the binding partners. With advanced tools of nuclear magnetic resonance the ground state of two proteins (ubiquitin and GB3) could be analyzed and could best be described as a conformational ensemble suggesting that the structural heterogeneity found in complexes is an intrinsic property of the protein already in the absence of the binding partners or substrates. We studied in addition the kinetic aspect of these and found that a major component happens on the 1 digit microsecond time scale. This time scale is difficult to access also by other techniques. Nevertheless, confirmation of the motion on this time scale could be found by temperature jump free electron laser X-ray scattering experiments conducted by Simone Techert and Thomas Burg based on our findings. In addition to the kinetic aspect of this one-digit microsecond motion, we investigated the possibility to enhancing the specificy of binding. Indeed this was possible by excluding conformations in the ground state ensemble which we showed could be useful for further developments of modulators of biologal funtion that do not interfer with the binding interface.