Fig. 1

Change in flexibility on modulator binding. Diagram showing the change in flexibility of a protein on modulator binding at an allosteric site. The solid line indicates the surface of the protein and circles show residues: non-filled circles represent residues that are part of pocket P and filled circles represent other residues. Dashed arrows represent the magnitude of the fluctuations of a residue about equilibrium. a shows the protein in the absence of a modulator. All residues can vibrate. b shows the effect of modulator M binding in pocket P. The residues in the pocket have restricted motion and are less able to vibrate around their equilibrium positions. Our method sought to approximate the effect of ligand binding by artificially restricting the flexibility of residues in a pocket using a higher spring constant in the elastic network