Bayesian Umbrella Quadrature Automates Free-Energy Calculations Across Diverse Molecular Systems and Processes

Area of Science:

• Computational Chemistry
• Molecular Dynamics Simulations
• Statistical Mechanics

Background:

• Biased sampling methods in molecular dynamics are crucial for overcoming timescale limitations in free-energy calculations.
• Current biasing protocols often require extensive manual fine-tuning, limiting their applicability across diverse systems.
• Automating these protocols is essential for robust and efficient free-energy landscape exploration.

Purpose of the Study:

• To develop an automated and robust free-energy calculation framework for molecular dynamics simulations.
• To address the limitations of manual fine-tuning in traditional biasing methods like Umbrella Sampling.
• To enhance the accuracy and efficiency of atomistic free-energy calculations across various systems.

Main Methods:

• Leveraged the Umbrella Integration formalism for automated free-energy calculation.
• Introduced Bayesian Umbrella Quadrature (BUQ), an iterative method selecting gradient samples to minimize posterior integral variance.
• Employed a noise-tolerant Gaussian process model for interpolation and variance reduction.

Main Results:

• Demonstrated accurate and robust free-energy calculations across a peptide conformational change, a water-to-ice phase transition, and a chemical reaction.
• Validated BUQ as an automated framework for free-energy calculations.
• Showcased the method's effectiveness in overcoming time scale limitations in molecular dynamics.

Conclusions:

• Bayesian Umbrella Quadrature (BUQ) offers an automated, accurate, and robust solution for free-energy calculations in molecular dynamics.
• The developed method simplifies the application of Umbrella Sampling, reducing the need for manual parameter tuning.
• BUQ enhances the accessibility and efficiency of studying complex atomistic phenomena through simulations.