Dissociation rates from single-molecule pulling experiments under large thermal fluctuations or large applied force.

Area of Science:

• Biophysics
• Physical Chemistry

Background:

• Current theories for single-molecule pulling experiments rely on Kramers' theory, which assumes high energy barriers relative to thermal energy (k_{B}T).
• Kramers' theory yields unphysical results in the low-barrier regime (comparable to k_{B}T), predicting increasing dissociation times with decreasing binding energy.

Purpose of the Study:

• To develop a theoretical framework that accurately describes Kramers' theory in the limit of large thermal fluctuations.
• To enable reliable extraction of dissociation rates from single-molecule experiments across a wide range of forces and binding energies.

Main Methods:

• Development of an amended theoretical framework.
• Validation through numerical simulations.
• Application to extract dissociation rates in single-molecule experiments.

Main Results:

• The proposed framework amends Kramers' theory for low-energy barriers (comparable to k_{B}T).
• Predictions from the new framework are physically meaningful and align with simulation results.
• The approach successfully extracts dissociation rates in single-molecule experiments over the entire range of applied forces.

Conclusions:

• The developed theoretical framework overcomes the limitations of Kramers' theory in the high thermal fluctuation regime.
• This advancement provides a physically sound method for analyzing single-molecule pulling experiments.
• The findings are broadly applicable to various experimental settings in biophysics.