Loading-device effects on the protein-unfolding mechanisms using molecular-dynamic simulations

Experimental force spectroscopy has been effectively utilized for measuring structural characterization of biomolecules and mechanical properties of biomaterials. Specifically, atomic force microscopy (AFM) has been widely used to portray biomolecular characterization in single-molecule experiment by observing the unfolding behavior of the proteins. Not only the experimental techniques enable us to characterize globular protein, but computational methods like molecular dynamics (MD) also gives insight into understanding biomolecular structures. To better comprehend the behavior of biomolecules, conditions such as pulling velocities and loading rates are put to the test, yet there are still limitations in understanding the unfolding behavior of biomolecules with the effect of different loading devices. In this study, we performed an all-atom MD and steered molecular dynamics (SMD) simulations considering different loading device effects such as “soft” and “stiff” to characterize the anisotropic unfolding behavior of ubiquitin protein. We found out the anisotropic unfolding pathways of the protein through the broken number of hydrogen bonds and geometric secondary structures of the biomolecule. Our study provides the importance for usage of various loading-devices on biomolecules when analyzing the structural compositions and the characteristics of globular biomolecules.