Molecular docking is an effective method to study protein-ligand interaction and recognition. The near-natural conformation formed in the process of intermolecular interaction is a conformation with extremely low binding free energy. Searching the conformation with extremely low energy quickly and accurately is very important for protein-ligand molecular docking. Protein-ligand molecular docking conformational search methods mainly include fast exhaustive search and heuristic search. If the ligand is a biological macromolecule, such as protein, RNA or DNA, the interaction region can appear anywhere on the molecular surface, so it is often necessary to conduct a global search, which can use fast exhaustive search to traverse various locations, or heuristic algorithms for approximate global search. If the ligand is a small molecular compound, the molecular docking often has a certain binding pocket, which can limit the search range of the conformational space, and the heuristic algorithm is usually used to search the limited region.
