Nonequilibrium path-ensemble averages for symmetric protocols.

Area of Science:

• Statistical Mechanics
• Computational Biophysics
• Physical Chemistry

Background:

• Nonequilibrium work relations enable free energy calculations from driven systems.
• Previous methods improved estimation using reverse processes (bidirectional approach).
• Symmetric protocols involve identical forward and reverse processes.

Purpose of the Study:

• Develop a rigorous statistical estimator for nonequilibrium path-ensemble averages using symmetric protocols.
• Evaluate the performance of this new estimator against existing methods.

Main Methods:

• Theoretical development of a novel statistical estimator for symmetric protocols.
• Testing the estimator on diverse model systems: potentials, biomolecular processes, and ion channels.
• Comparison with unidirectional and bidirectional estimators.

Main Results:

• The new symmetric estimator outperforms existing methods in free energy reconstruction from symmetric protocols, showing faster convergence and reduced error.
• Bidirectional estimators with asymmetric protocols generally achieve better performance than symmetric protocols for the same simulation time.
• The symmetric estimator demonstrates comparable performance to a unidirectional protocol of half the length.

Conclusions:

• The developed symmetric estimator is a valuable tool for free energy calculations, particularly when bidirectional approaches are infeasible.
• For maximum efficiency, bidirectional estimators with asymmetric protocols are often preferred.
• The findings offer insights into optimizing computational strategies for free energy estimation in complex systems.