Lattice model studies of force-induced unfolding of proteins

We probe the general characteristics of force-induced unfolding of proteins using lattice models. The computations show that the experimental observat ions. such as the shape of the force-extension curves and hysteresis, are q ualitatively reproduced using the coarse-grained models. Force hysteresis, which occurs because the structural relaxation times are longer than the ti me scales for dissipation of stored mechanical energy, strongly depends on the rate of application of force or the pulling speed. As a result, refoldi ng is not spontaneous, when force is decreased after fully extending the po lypeptide chain. Most importantly, we show that the distribution of unfoldi ng free energy barriers in the absence of force can be obtained using the d ynamics of force-induced unfolding. This key result immediately suggests th at dynamic single molecule force spectroscopy can be used to directly measu re the folding free energy landscape of proteins.