Search for European Projects

Intramolecular force mapping of enzymes in action: the role of strain in motor mechanisms (forcemap)
Start date: Sep 1, 2008, End date: Aug 31, 2014 PROJECT  FINISHED 

A fundamental but unexplored problem in biology is whether and how enzymes use mechanical strain during their functioning. It is now evident that the knowledge of atomic structures and chemical interactions is not sufficient to understand the intricate mechanisms underlying enzyme specificity and efficiency. Several lines of evidence suggest that mechanical effects play crucial roles in enzyme activity. Therefore we aim to create detailed force maps that reveal how the intramolecular distribution of mechanical strains changes during the enzyme cycle and how these rearrangements drive the enzyme processes. The applicability of current nanotechniques for the investigation of this problem is limited because they do not allow simultaneous measurement of mechanical and enzymatic parameters. Thus we seek to open new avenues of research by developing site-specific sensors and passive or photoinducible molecular springs to measure force-dependent chemical/structural changes with high spatiotemporal resolution in myosin. Since force perturbations occur very rapidly, we are able to combine experimental studies with quasi-realistic in silico simulations to describe the physical background of enzyme function. We expect that our research will yield fundamental insights into the role of intramolecular strains in enzymes and thus greatly aid the design and control of enzyme processes (specificity, activity, regulation). Our studies may also lead to new paradigms in the understanding of motor systems.
Up2Europe Ads