Free energy for protein folding from nonequilibrium simulations using the Jarzynski equality

Area of Science:

• Biophysics
• Computational Chemistry
• Statistical Mechanics

Background:

• The Jarzynski equality (JE) provides a theoretical framework to calculate equilibrium free energy differences from nonequilibrium work measurements.
• Estimating protein free energy is crucial for understanding protein folding and function.

Purpose of the Study:

• To test the applicability and accuracy of the Jarzynski equality for estimating protein free energy differences.
• To investigate the impact of simulation conditions on the reliability of JE-based free energy calculations.

Main Methods:

• Utilized molecular dynamics simulations to model protein unfolding by pulling atoms apart.
• Employed a simplified protein model with independently computable equilibrium properties.
• Analyzed the work performed during fast, nonequilibrium pulling processes.

Main Results:

• Demonstrated that the Jarzynski equality can accurately estimate free energy from nonequilibrium simulations.
• Highlighted the critical importance of correctly selecting the ensemble of pulled states for accurate results.
• Showed that free energy from forced unfolding may differ from solution-based measurements.

Conclusions:

• The Jarzynski equality is a viable method for free energy estimation in biophysical systems.
• Careful experimental or simulation design is necessary to overcome challenges in applying the JE to forced unfolding.
• Discrepancies between simulation-derived and solution-based free energies warrant further investigation.