Protein – ligand interactions
Not always, but sometimes one wants to flatten the interactions between a protein and a ligand. The aim is to unclutter the three-dimensional (3D) information to a 2D image. With such visualizations, the advantages is that one gets to see the various interactions without any of them getting buried, and concentrate on the crucial ones that are the key to protein-ligand interactions. The situations where these 2D representations are used are broadly of two areas:
- Plotting the interactions of protein-ligand complexes in the existing data (from PDB database)
- Plotting the interactions between a protein and a potential drug/small molecule from a molecular docking result. Again, the input could be from a single small molecule docking or from a virtual screening.
In this post, we will see three tools that help us in achieving the goal of plotting protein-ligand interactions.
LIGPLOT – For many years, Ligplot (1) has been the choice for plotting 2D interactions. Infact, the database pdbsum makes ligplot images for a given protein-ligand interactions. The main two things shown are the hydrogen bonds and hydrophobic interactions.
Hydrogen bonds are indicated by dashed lines between the atoms involved, while hydrophobic contacts are represented by an arc with spokes radiating towards the ligand atoms they contact. The contacted atoms are shown with spokes radiating back.
PoseView – This is a new tool that came out two years ago (2). It has Ligplot-like image generation but it has more features than Ligplot.
The 2D depiction shows hydrogen bonds as dashed lines between the interaction partners on either side. Hydrophobic interactions are illustrated as smooth contour lines between the respective amino acids and the ligand.
Recently PDB database incroporated poseview with the structures that are present. So, one can get the 2D plots straight away from PDB itself in the Ligand section of each protein, for example here. The web-interface for PoseView can be accessed here.
BINding ANAlyzer (BINANA) – This is probably the most recent protein-ligand representation tool (3). Although, not exactly a 2D plotting tool, it has more features than Ligplot or PoseView, namely it can plot electrostatic interactions, pi pi stacking, cation-pi interactions, and more. The only downside is that it needs the input in .PDBQT format. This can be obtained via AutoDock Tools. The output can be visualized via VMD, thus making the 2D back into 3D bu with distinguishable features.
1. Wallace AC, Laskowski RA, & Thornton JM (1995). LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein engineering, 8 (2), 127-34 PMID: 7630882
2. Stierand, K., & Rarey, M. (2010). Drawing the PDB: Protein−Ligand Complexes in Two Dimensions ACS Medicinal Chemistry Letters, 1 (9), 540-545 DOI: 10.1021/ml100164p
3. Durrant, J., & McCammon, J. (2011). BINANA: A novel algorithm for ligand-binding characterization Journal of Molecular Graphics and Modelling, 29 (6), 888-893 DOI: 10.1016/j.jmgm.2011.01.004