Reconstructing multiple free energy pathways of DNA stretching from single molecule experiments

Area of Science:

• Biophysics
• Computational Biology
• Molecular Dynamics

Background:

• Free energy landscapes are crucial for understanding protein and nucleic acid folding dynamics.
• Jarzynski's equality reconstructs these landscapes from single molecule force measurements (stretching data).

Purpose of the Study:

• To demonstrate the utility of the Crooks fluctuation theorem for reconstructing full free energy landscapes.
• To show how Jarzynski's equality can identify individual folding pathways when multiple exist.

Main Methods:

• Utilized the Crooks fluctuation theorem with both stretching and relaxation force data from single molecule force measurements.
• Applied Jarzynski's equality to analyze distinct work distributions for multiple folding pathways.
• Reconstructed the overstretching transition of poly(dA) as a model system.

Main Results:

• The Crooks fluctuation theorem successfully reconstructs full free energy landscapes, similar to Jarzynski's equality.
• The theorem offers more rapid convergence for free energy estimates in reversible processes.
• Jarzynski's equality effectively identified individual free energy pathways in complex folding scenarios.

Conclusions:

• The nonequilibrium work theorem, coupled with single molecule force measurements, provides a comprehensive view of free energy landscapes.
• This approach enhances the study of biomolecular folding dynamics and mechanisms.