Mechanical unfolding revisited through a simple but realistic model.

Single-molecule experiments and their application to probe the mechanical resistance and related properties of proteins provide a new dimension in our knowledge of these important and complex biological molecules. Single-molecule techniques may not have yet overridden solution experiments as a method of choice to characterize biophysical and biological properties of proteins, but have stimulated a debate and contributed considerably to bridge theory and experiment. Here we demonstrate this latter contribution by illustrating the reach of some theoretical findings using a solvable but nontrivial molecular model whose properties are analogous to those of the corresponding experimental systems. In particular, we show the relationship between the thermodynamic and the mechanical properties of a protein. The simulations presented here also illustrate how forced and spontaneous unfolding occur through different pathways and that folding and unfolding rates at equilibrium cannot in general be obtained from forced unfolding experiments or simulations. We also study the relationship between the energy surface and the mechanical resistance of a protein and show how a simple analysis of the native state can predict much of the mechanical properties of a protein.