Time-asymmetric fluctuation theorem and efficient free-energy estimation.

Area of Science:

• Statistical mechanics
• Computational physics
• Physical chemistry

Background:

• Computing free-energy differences (ΔF) in high-dimensional systems is challenging.
• Accurate ΔF calculation is vital for applications like drug discovery.
• An unconventional work definition by Vaikuntanathan and Jarzynski (2008) satisfies a microscopic fluctuation theorem.

Purpose of the Study:

• To demonstrate the utility of a time-asymmetric microscopic fluctuation theorem for free-energy estimation.
• To develop an efficient and simple algorithm for calculating ΔF.
• To improve upon existing methods for free-energy calculations.

Main Methods:

• Utilized an unconventional definition of work satisfying a microscopic fluctuation theorem.
• Employed counterdiabatic protocols for zero-variance work measurements.
• Developed a neural-network-free adaptive time-asymmetric protocol optimization algorithm.

Main Results:

• The developed algorithm yields ΔF estimates with significantly lower mean squared error compared to standard methods.
• Demonstrated orders of magnitude improvement in accuracy over generic linear interpolation protocols.
• Showcased the effectiveness of the time-asymmetric fluctuation theorem for efficient free-energy estimation.

Conclusions:

• The novel adaptive protocol optimization algorithm provides a highly efficient and accurate method for free-energy estimation.
• This approach offers a practical alternative to complex and computationally expensive methods.
• The findings have significant implications for accelerating drug discovery and other fields requiring precise free-energy calculations.