Mechanical Unfolding of Macromolecules Coupled to Bond Dissociation

Single-molecule force spectroscopy has become a powerful tool to investigate molecular mechanisms in biophysics and materials science. In particular, the new field of polymer mechanochemistry has emerged to study how tension may induce chemical reactions metalloprotein rubredoxin coupled to dissociation of iron-sulfur bonds in a macromolecule. A rich example is the mechanical unfolding of the that has recently been studied in detail by atomic force microscopy. Here, we present a simple molecular model composed of a classical all atom force field description, implicit solvation, and steered molecular dynamics simulation to describe the mechanical properties and mechanism of forced unfolding coupled to covalent bond dissociation of macromolecules. We apply this model and test it extensively to simulate forced rubredoxin unfolding, and we dissect the sensitivity of the calculated mechanical properties with model parameters. The model provides a detailed molecular explanation of experimental observables such as force-extension profiles and contour length increments. Changing the points of force application along the macromolecule results in different unfolding mechanisms, characterized by disruption of hydrogen bonds and secondary protein structure, and determines the degree of solvent access to the reactive center. We expect that this molecular model will be broadly applicable to simulate (bio)polymer mechanochemistry. (AU)