Ligand docking and binding site analysis with PyMOL and Autodock/Vina

Abstract

Docking of small molecule compounds into the binding site of a receptor and estimating the binding affinity of the complex is an important part of the structure-based drug design process. For a thorough understanding of the structural principles that determine the strength of a protein/ligand complex both, an accurate and fast docking protocol and the ability to visualize binding geometries and interactions are mandatory. Here we present an interface between the popular molecular graphics system PyMOL and the molecular docking suites Autodock and Vina and demonstrate how the combination of docking and visualization can aid structure-based drug design efforts.

Fig. 1

Definition of a docking box around a reference ligand. Position, size and visualization properties can be adjusted with the plugin

Fig. 2

Selection of sidechains within the binding site for the setup of docking runs with flexible sidechains

Fig. 3

Autodock grid maps displayed with different contour levels. a Map for interactions of aliphatic carbon atoms at contour level 5 kcal/mol. b Same map at contour level −0.3 kcal/mol. c Hydrogen bond donor map at contour level −0.5 kcal/mol

Fig. 4

Analysis of docking poses. Left: PyMOL viewer with displayed docking poses. Right: Pose viewer page of the plugin. Poses from multiple docking runs may be analyzed simultaneously using an intuitive notebook layout

Fig. 5

Virtual screening analysis. A ranked list of docked ligands is generated automatically and it can be exported in different data formats. Additionally, docking poses from different ligands can be exported in a single file