FEP-SPell-ABFE: An Open-Source Automated Alchemical Absolute Binding Free-Energy Calculation Workflow for Drug Discovery

• DOI: 10.1021/acs.jcim.4c01986
• Publication Date: 2025-03-03T16:20:32Z
• Authors: Pengfei Li; Tingting Pu; Ye Mei
• Keywords: Spell

The binding affinity between a drug molecule and its target, measured by the absolute free energy (ABFE), is crucial factor in lead discovery phase of development. Recent research has highlighted potential silico ABFE predictions to directly aid development allowing for ranking prioritization promising candidates. This work introduces an open-source Python workflow called FEP-SPell-ABFE, designed automate calculations with minimal user involvement. requires only three key inputs: receptor protein structure PDB format, candidate ligands SDF configuration file (config.yaml) that governs both molecular dynamics simulation parameters. It produces ranked list along their energies comma-separated values (CSV) format. leverages SLURM (Simple Linux Utility Resource Management) automating task execution resource allocation across modules. A usage example several benchmark systems validation are provided. FEP-SPell-ABFE workflow, practical example, publicly accessible on GitHub at https://github.com/freeenergylab/FEP-SPell-ABFE, distributed under MIT License.