There is a large number of possible fragment combinations. A small perturbation of the previous fragment conformation would cause great difference in activity. In order to find the lowest binding energy on the Potential energy surface (PES) between fragments and a receptor pocket, the scoring function calculation would be performed for every step of conformation change of the fragments derived from every type of possible fragments combination. Since this requires a large amount of computation, using different tricks may use less computing power and let the program work more efficiently. When a ligand is inserted into the pocket site of a receptor, groups on the ligand that bind tightly with the receptor should have the highest priority in finding their lowest-energy conformation. This allows us to put several seeds into the program at the same time and optimize the conformation of those seeds that form significant interactions with the receptor, and then connect those seeds into a continuous ligand in a manner that make the rest of the ligand have the lowest energy. The pre-placed seeds ensure high binding affinity and their optimal conformation determines the manner in which the ligand will be built, thus determining the overall structure of the final ligand. This strategy efficiently reduces the calculation burden for fragment construction. On the other hand, it reduces the possibility of the combination of fragments, which reduces the number of possible ligands that can be derived from the program. The two strategies above are widely used in most structure-based drug design programs. They are described as «Grow» and «Link». The two strategies are always combined in order to make the construction result more reliable.