Molecular docking has emerged as a cornerstone of modern drug discovery and development. By predicting the binding orientation and affinity of small molecules to their biological targets, docking enables rational design of therapeutics, accelerates lead identification, and reduces the reliance on resource-intensive experimental approaches. This review provides a comprehensive overview of molecular docking techniques, including fundamental principles, algorithms, scoring functions, and software tools. Emphasis is placed on the applications of docking in hit identification, lead optimization, drug repurposing, and mechanistic studies. Additionally, the limitations of docking methodologies are critically discussed, with special attention to challenges in protein flexibility, solvation models, and scoring accuracy. Finally, future perspectives are explored, highlighting the integration of artificial intelligence, molecular dynamics, and high-throughput screening in advancing the accuracy and predictive power of docking. Collectively, this review underscores the indispensable role of molecular docking in structure-based drug discovery.
Shende et al. (Fri,) studied this question.