How docking programs work

Abstract

Protein–ligand docking simulations are of central interest for computer-aided drug design. Docking is also of pivotal importance to understand the structural basis for protein–ligand binding affinity. In the last decades, we have seen an explosion in the number of three-dimensional structures of protein–ligand complexes available at the Protein Data Bank. These structures gave further support for the development and validation of in silico approaches to address the binding of small molecules to proteins. As a result, we have now dozens of open source programs and web servers to carry out molecular docking simulations. The development of the docking programs and the success of such simulations called the attention of a broad spectrum of researchers not necessarily familiar with computer simulations. In this scenario, it is essential for those involved in experimental studies of protein–ligand interactions and biophysical techniques to have a glimpse of the basics of the protein–ligand docking simulations. Applications of protein–ligand docking simulations to drug development and discovery were able to identify hits, inhibitors, and even drugs. In the present chapter, we cover the fundamental ideas behind protein–ligand docking programs for non-specialists, which may benefit from such knowledge when studying molecular recognition mechanism.