Good practices in free-energy calculations.

Area of Science:

• Computational chemistry
• Molecular modeling

Background:

• Free-energy calculations are increasingly vital for predictive research.
• Reliability of these calculations can be enhanced by adhering to established best practices.
• Theoretical advancements are not always integrated into common computational platforms.

Purpose of the Study:

• To discuss current best practices for free-energy calculations.
• To demonstrate how to improve the accuracy and precision of free-energy estimates.
• To highlight methods for obtaining meaningful error bounds.

Main Methods:

• Utilizing free energy perturbation (FEP) and nonequilibrium work (NMW) methods.
• Monitoring probability distributions during state transformations.
• Performing calculations bidirectionally and stratifying the reaction pathway.
• Selecting appropriate paradigms and algorithms for state transformations.

Main Results:

• Adherence to best practices leads to markedly improved free-energy estimates.
• Little to no additional computational cost is required for significant gains.
• Meaningful error estimates can be reliably bounded.
• Enhanced accuracy and precision are achieved through methodological improvements.

Conclusions:

• Implementing best practices in free-energy calculations is crucial for reliable predictions.
• Simple yet effective strategies can substantially improve computational results.
• The integration of theoretical developments into practical workflows is essential.