A3FE

A3FE implements a fully automated workflow for alchemical absolute binding free energy calculations, reducing computational cost and human intervention through adaptive algorithms.

Key Features:

• Automated λ Window Selection: Automatically selects intermediate states with consistent overlap for alchemical transformations.
• Ensemble-Based Equilibration Detection: Detects equilibration using a paired t-test between free energy estimates at initial and final portions of an ensemble of runs.
• Adaptive Sampling Allocation: Adaptively allocates sampling time based on inter-replicate statistics.
• Nonadaptive Equivalent Accuracy: Produces equivalent results to nonadaptive schemes across diverse test systems while often accelerating equilibration.

Scientific Applications:

• Drug Discovery: Enables efficient alchemical absolute binding free energy calculations for computational drug design.
• Protein-Ligand Binding: Calculates absolute binding free energies for diverse molecular systems.

Methodology:

The workflow employs automated selection of λ windows, ensemble-based detection of equilibration via paired t-tests between initial and final free energy estimates across replicate runs, and adaptive allocation of sampling time based on inter-replicate statistics.