Structure-based drug design 2. With the increasing computational power, structure-based drug design is playing more important role to guide drug discovery. The objective of molecular docking is to obtain the lowest free energy structures for the receptor-ligand complex. The resulted ligands will provide the leads that will be studied as drug candidates. For the description of receptor and ligand, the coordinates of each atom are obtained through X-ray crystallography, NMR and homology modeling with certain accuracy.
Successful docking requires shape complementarity of the ligand and receptor.
Therefore, the shape is the first thing that should be considered in docking problem. To juxtapose the ligand and the receptor, one has to search the configuration and conformational space of the ligand and the receptor. There are two classes of searching method. MD combines the configuration and conformation transition smoothly and MD can reveal dynamic information of the docking process. MD is not wildly used in industry because the complex topography and multiple minima of molecular potential surface often lead to long run time.