Multiple barriers in forced rupture of protein complexes

Area of Science:

• Biophysics
• Molecular Dynamics
• Biochemistry

Background:

• Dynamic force spectroscopy (DFS) analyzes biomolecular complex rupture forces.
• Interpreting force-loading rate curves requires understanding free energy profiles.

Purpose of the Study:

• Provide a criterion to differentiate between single-barrier and multi-barrier models for biomolecular unbinding.
• Analyze experimental DFS data to infer the nature of the energy landscape.

Main Methods:

• Utilized dynamic force spectroscopy (DFS) to measure rupture forces.
• Applied a theoretical framework relating rupture force, loading rate, and energy landscape exponents.
• Analyzed experimental data from biotin-ligand and LFA-1/ICAM complexes.

Main Results:

• Developed a criterion based on the exponent ν derived from force-loading rate relationships.
• Demonstrated that ν values < 0.5, observed in biotin-ligand and LFA-1/ICAM complexes, indicate multi-barrier energy landscapes.
• Showed that single-barrier models predict 0.5 ≤ ν ≤ 1.

Conclusions:

• The observed curvature in DFS data for specific biomolecular complexes suggests multi-barrier energy landscapes.
• The criterion based on the exponent ν effectively distinguishes between single and multiple energy barriers in unbinding processes.
• This work provides a method to infer the complexity of molecular unbinding pathways from experimental force spectroscopy data.