Protein–ligand docking

Protein–ligand docking is a molecular modelling technique. The goal of protein–ligand docking is to predict the position and orientation of a ligand (a small molecule) when it is bound to a protein receptor or enzyme. Pharmaceutical research employs docking techniques for a variety of purposes, most notably in the virtual screening of large databases of available chemicals in order to select likely drug candidates.

Several protein–ligand docking software applications are available, such as AutoDock, rDock (free and opensource) or EADock. There are also web service (Molecular Docking Server, SwissDock) that calculate the site, geometry and energy of small molecules interacting with proteins.

Protein flexibility
Computational capacity has increased dramatically over the last decade making possible the use of more sophisticated and computationally intensive methods in computer-assisted drug design. However, dealing with receptor flexibility in docking methodologies is still a thorny issue. The main reason behind this difficulty is the large number of degrees of freedom that have to be considered in this kind of calculations. However, neglecting it leads to poor docking results in terms of binding pose prediction in real-world settings.