Characterization of mechanical unfolding intermediates of membrane proteins by coarse grained molecular dynamics simulation

Highlights: • Coarse-grained model demonstrated forced unfolding process of a membrane protein. • The simulations reproduced experimental force-distance curves. • The force peak formation mechanism was investigated. Single-molecule force spectroscopy by atomic force microscopy allows us to get insight into the mechanical unfolding of membrane proteins, and a typical experiment exhibits characteristic patterns on the force distance curves. The origin of these patterns, however, has not been fully understood yet. We performed coarse-grained simulation of the forced unfolding of halorodopsin, reproduced the characteristic features of the experimental force distance curves. A further examination near the membrane-water interface indicated the existence of a motif for the force peak formation, i.e., the occurrence of hydrophobic residues in the upper interface region and hydrophilic residues below the lower interface region.