ALISE, an innovation from our research group, is the Automated Ligand Searcher—a crucial component seamlessly integrated into the VIKING web platform. It stands as a robust virtual screening tool tailored explicitly for drug discovery. ALISE specializes in estimating the binding free energy of potential drug candidates targeted toward specific receptors. This estimation involves three sequential stages: docking, molecular dynamics simulation, and free energy perturbation. Each stage operates with increasing precision but demands progressively higher computational resources. ALISE optimizes the selection process by advancing only the most promising candidates, exhibiting favorable binding energies to subsequent stages. ALISE is an amalgamation of 10 discrete programs into a unified web application that distinguishes it. This amalgamation transforms complex methodologies into an accessible tool suitable for seasoned experts and drug development newcomers. ALISE is a sophisticated aid that simplifies and enhances the quest for potential pharmaceutical agents.