Figure 3.

Protein nanomechanics 101. a Simplified representation of a protein under mechanical force, which depicts a random coil region as a spring and a folded domain as a loop. The random coil region adapts its length to force in an elastic manner (states 1 through 3), while the folded domain only unfolds at high forces (states 2→3). b States 1 through 3 in panel (a) are identified in a simulated single-molecule force-extension plot. c Graphical representation of force-polymer length relationship according to the worm-like chain model. d Simple two-state free energy diagram underlying protein unfolding in the bulk. Please note that the contour length of the folded and unfolded states is very similar. The position of the transition state (ts) is indicated. e Simple free energy diagrams of a protein at 0 and 10 pN pulling force considering extension as the reaction coordinate. Extended states can only be observed at forces that overcome the tendency of polypeptides to undergo hydrophobic collapse (i.e., there is no free energy minimum corresponding to an extended state at 0 pN). Since the folded/unfolded states have very similar contour lengths, they cannot be observed directly in single-molecule pulling experiments. f Graphical representation of the Bell-Evans model, which considers that the height of the energy barrier decreases by F∆x when force is applied in the direction of molecular extension. The position of the transition state (ts) is indicated.