Path-breaking schemes for nonequilibrium free energy calculations

Area of Science:

• Computational Chemistry
• Statistical Mechanics
• Biophysics

Background:

• Unidirectional nonequilibrium simulations are crucial for calculating free energy differences using Jarzynski's equality.
• A major limitation is the extensive number of simulations required for convergence of the work exponential average.
• Current methods necessitate long simulation trajectories, increasing computational cost.

Purpose of the Study:

• To introduce a novel path-breaking approach for enhancing the efficiency of unidirectional nonequilibrium simulations.
• To reduce the computational time required for accurate free energy difference calculations.
• To improve the convergence of work exponential averages in Jarzynski's equality applications.

Main Methods:

• Implementation of path-breaking schemes involving periodic checks of dissipated work during pulling trajectories.
• Two strategies are employed: breaking trajectories exceeding a work threshold or probabilistically based on dissipated work.
• The method is validated on diverse processes: helix-coil transition of deca-alanine and methane molecule pulling in water.

Main Results:

• Significant reduction in computer time, by factors of 2 to over 10, for the simulated processes.
• Demonstrated efficiency is influenced by process type, checkpoint frequency, and pulling rate.
• Successful application to both biomolecular (deca-alanine) and simple molecular (methane in water) systems.

Conclusions:

• Path-breaking schemes offer a substantial improvement in the computational efficiency of free energy calculations via Jarzynski's equality.
• The developed method effectively reduces the number of necessary simulation realizations.
• This approach provides a computationally advantageous alternative for various molecular simulation studies.