BFEE2: Automated, Streamlined, and Accurate Absolute Binding Free-Energy Calculations

Area of Science:

• Computational chemistry
• Molecular modeling
• Biophysics

Background:

• Accurate absolute binding free-energy estimation is crucial for drug discovery and molecular design.
• Traditional methods require significant human intervention, leading to potential errors and reproducibility issues.
• Automating these calculations is essential for broader accessibility and efficiency.

Purpose of the Study:

• To introduce version 2.0 of the Binding Free Energy Estimator (BFEE2), a software tool designed to automate and standardize absolute binding free-energy calculations.
• To reduce human intervention in alchemical and geometrical free-energy estimation workflows.
• To enhance the reproducibility and accessibility of in silico binding free-energy calculations for a wider range of users.

Main Methods:

• BFEE2 implements standardized alchemical and geometrical workflows for free-energy calculations.
• The software supports major academic force fields (CHARMM, Amber, OPLS, GROMOS) and generates input files for NAMD and Gromacs.
• Automated post-treatment and simulation convergence monitoring are integrated features.

Main Results:

• BFEE2 successfully automates complex subprocesses involved in absolute binding free-energy estimation.
• The tool minimizes the need for user expertise in defining collective variables, preparing inputs, and performing post-treatments.
• BFEE2 ensures complete reproducibility of results across various protein-ligand and host-guest systems.

Conclusions:

• BFEE2 is a versatile and user-friendly tool for accurate in silico absolute binding free-energy calculations.
• The automation provided by BFEE2 significantly streamlines the workflow, making it accessible to non-experts.
• BFEE2 facilitates a broad range of applications in molecular design and drug discovery by enhancing accuracy and reproducibility.