Identifying ligand interactions with PDBe-KB protein pages¶

Task 1 (ligand images)¶

Navigate to the ligands section of the protein page and look at the list of ligand images

• Which ones are most commonly found bound to this structure in PDB entries?

• Can you group these ligands based on visual similarity (I.e. they look like similar chemical structures)? Note: this does not have to accurate matching - structures with rings, structures with extended chains etc. is enough.

Task 2 (interaction sites)¶

Look at the ProtVista viewer for the ligands section.

• Can you group these ligands based on similar patterns of binding?

• Does this correlate with the groups you defined in Task 1? Which ligands differ from these groups? Is there anything clear reason for this?

• Which method of grouping the ligands did you find easier?

Task 3 (viewing ligands)¶

Select one of the ligands in the image section and click on the ‘3D view’. This will show an example of this ligand binding site, with the ligand itself shown with purple bonds and the surrounding amino acids shown in grey. If this example is an X-ray crystallography entry then the density maps will also be shown.

• Can you find all of the interacting amino acids (by nearby atoms) in the 3D viewer? Note: Hovering over the atom will show the amino acid in the top left.

• Can you match these interacting amino acids to the ones shown to be interacting in the ProtVista viewer? Note: it might help to have one of you looking at the viewer, and the other at ProtVista.

• Does the ligand fit well to the density?

• Are there any regions where it fits poorly?

Task 4 (amino acid properties)¶

In the 3D view, click on the PDB ID at the top right (above the menu). This will take you to the entry page for that example. Once you get to the entry page, click on the ligand image for the ligand ID you were viewing. This will take you to the interaction page that is specific for this ligand in this entry.

This page has 2 sections below displaying binding site data. On the left is an image displaying the ligand interactions with amino acids. There are 2 types of interactions shown. Amino acids that make non-specific interactions (e.g. van der Waals, hydrophobic) are displayed only as text with red dashes. Amino acids that make specific interactions (i.e. hydrogen bonds) are displayed with gold sticks with dashed green lines highlighting the hydrogen bonds.

• Which amino acids make non-specific contacts with the ligand?

• Which amino acids hydrogen bond to the ligand?

• Do the different regions of the ligand make different types of interactions?

Look at the viewer on the right of the page. This displays the binding site in 3D like in the protein page viewer, however this page has our brand new Mol* viewer. By default, this is set to rotate to show the binding site from different orientations.

• Can you identify the interacting atoms in the 3D viewer?

• Is this easier or more difficult than using the interaction image?

Note: we will soon be making the 2D interaction view into an interactive component that will highlight the amino acids in the 3D view when you click on the interaction view, so keep an eye out!