Enzymes are programmable, viscoelastic machines

As they perform their biological functions, proteins typically undergo large conformational changes that are associated with mechanical deformation (e.g. allostery). Thus, specific regions in the protein that are flexible, viscoelastic elements must have emerged through evolution. A simple theory by Tlusty and coworkers indicates that such regions can be identified by amino acid rearrangement upon binding (i.e., shear motion). We have tested the concept in an experimental nano-rheology study of the enzyme Guanylate Kinase linking shear, large-scale motions, and catalytic function. Mutations of even a single amino acids directed at these flexible regions are found to impact on viscoelastic parameters as well as on functionality. Taken together, the findings we present paint a physical picture of proteins as viscoelastic machines with sequence-encoded specifications.