ALCHEMD Enables Automated Free Energy Perturbation-Relative Binding Free Energy Calculations on Standard Personal Computers

ALCHEMD represents an integrated, automated, efficient, and user-friendly software for FEP-RBFE calculations, with the capability to complete dozens of pair calculations within a single day on a standard personal computer equipped with commodity GPU (e.g., RTX 4060Ti). Through a streamlined workflow that encompasses system setup, molecular dynamics simulations with enhanced adaptive sampling, and free energy analysis, ALCHEMD ensures minimal user intervention and near-zero cost per trial. This makes the software particularly attractive to chemists seeking to refine highly potent ligands or lead compounds without relying on large-scale HPC clusters or extensive computational expertise.