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free-energy-calculations

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Performs alchemical free-energy calculations including relative binding free energy (RBFE / FEP+) and absolute binding free energy (ABFE) via OpenFE, FEP+, GROMACS, AMBER pmemd, and OpenMM with explicit lambda scheduling, soft-core potentials, MBAR/BAR analysis, cycle-closure validation, and protocol-appropriate enhanced sampling. Compares ML alternatives (Boltz-2 affinity, DeepDock). Use when ranking analogs by binding affinity beyond docking accuracy, performing prospective lead optimization, or validating SAR predictions.

When to use

• relative binding free energy (RBFE)
• absolute binding free energy (ABFE)
• ranking analogs by binding affinity
• prospective lead optimization
• validating SAR predictions
• selectivity analysis (target vs off-target)
• cross-scaffold ranking
• congeneric lead-optimization sets

When not to use

• docking input poses
• pose validation before FEP
• ions / metal centers
• novel chemotypes for ML affinity

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