Anisotropic Friction in a Ligand-Protein Complex

The effect of an externally applied directional force on molecular friction is so far poorly understood. Here, we study the force-driven dissociation of the ligand-protein complex biotinstreptavidin and identify anisotropic friction as a not yet described type of molecular friction. Using AFM-based stereographic single molecule force spectroscopy and targeted molecular dynamics simulations, we find that the rupture force and friction for biotinstreptavidin vary with the pulling angle. This observation holds true for friction extracted from Kramers' rate expression and by dissipation-corrected targeted molecular dynamics simulations based on Jarzynski's identity. We rule out ligand solvation and protein-internal friction as sources of the angle-dependent friction. Instead, we observe a heterogeneity in free energy barriers along an experimentally uncontrolled orientation parameter, which increases the rupture force variance and therefore the overall friction. We anticipate that anisotropic friction needs to be accounted for in a complete understanding of friction in biomolecular dynamics and anisotropic mechanical environments.

Automated summary

In this study, the rupture force and friction of the biotin-streptavidin complex under a externally applied force were investigated using AFM-based single molecule force spectroscopy and molecular dynamics simulations. Anisotropic friction, arising from an experimentally uncontrolled orientation parameter, was identified. The study suggests that anisotropic friction should be taken into account for a complete understanding of friction in biomolecular dynamics and anisotropic mechanical environments.