What is molecular docking and how is it used in drug discovery?

Molecular docking predicts the preferred orientation and binding affinity of a small molecule (ligand) to a protein target. The process involves: 1) Protein preparation - add hydrogens, assign charges, define binding site. 2) Ligand preparation - generate 3D conformers, assign charges. 3) Docking - search algorithms (genetic algorithms, Monte Carlo, incremental construction) sample ligand poses while scoring functions estimate binding affinity. 4) Scoring - physics-based (force fields), empirical, or knowledge-based functions rank poses. Popular tools include AutoDock, Glide, GOLD, and MOE. In drug discovery, docking enables virtual screening of compound libraries, lead optimization, and understanding of binding mechanisms, significantly reducing experimental screening costs.