Mohsen Soroushmanesh Hi

Of course, You have to dock any single ligand to a macromolecule but each software has its algorithm for docking. So, it generates possible conformations during ligand preparation. For example, you use the AutoDOCK tool or AutoDOCKVINA so it produces 10 docked poses and which one is more active with protein will show on the top list.

Thanks @Waseem Ahmad Ansari

Yes, it is possible to perform multiple dockings of the same ligand on a single macromolecule. This approach is often referred to as "re-docking" or "iterative docking." In this process, the output conformation obtained from one docking run can be used as the starting point for subsequent docking runs. The idea is to refine the ligand's orientation and conformation in the binding site by iteratively adjusting its position based on the previous results. Iterative docking can be beneficial for improving the accuracy of the predicted binding pose and affinity. However, it's important to note that the success of this approach depends on the accuracy of the initial docking and the specific algorithm or software used. Some molecular docking tools allow for this iterative or re-docking process, enabling users to refine the ligand's position and better explore the conformational space within the binding site.Iterative docking can be particularly useful when dealing with flexible ligands or when attempting to predict subtle changes in binding modes. However, it's essential to consider the limitations of the specific docking software and scoring functions being used, as well as the potential impact of inaccuracies in the initial docking poses on the iterative process. Additionally, the success of iterative docking relies on the ability of the algorithm to explore relevant conformational space effectively.

Thank you for your response. Is it possible to dock one ligand, and then, taking into account the influence of the first ligand, proceed to dock the second ligand (same ligand) in the presence of the first one? @Sargol Mazraedoost