Before searching for the optimal configuration of the ligand molecule the protein and ligand are separated by some physical distance. The process of finding the optimal configuration for the ligand involves some transformations, such as rotation and movement in space, and a change in the conformation of the ligand due to the presence of rotational chemical bonds linking rigid fragments. Each transformation changes the energy and it must be recalculated for the new ligand configuration. Thus, the search space in our task has the dimension M + 6, where M is the number of rotatable bonds in the ligand molecule. These rotatable bonds connect rigid fragments.