Biological function relies on the fact that biomolecules can switch between different conformations and aggregation states. Such transitions involve a rearrangement of parts of the biomolecules involved that act as dynamic domains. The reliable identification of such domains is thus a key problem in biophysics. In this work we present a method to identify semi-rigid domains based on dynamical data that can be obtained from molecular dynamics simulations or experiments. To this end the average inter-atomic distance- deviations are computed. The resulting matrix is then clustered by a constrained quadratic optimization problem. The reliability and performance of the method are demonstrated for two artificial peptides. Furthermore we correlate the mechanical properties with biological malfunction in three variants of amyloidogenic transthyretin protein, where the method reveals that a pathological mutation destabilizes the natural dimer structure of the protein. Finally the method is used to identify functional domains of the GroEL-GroES chaperone, thus illustrating the efficiency of the method for large biomolecular machines.
