UCSF Chimera - preparing ligands

UCSF Chimera is a program originally written as a molecular viewer. Nowadays, one can do a lot of other things; it is for instance totally integrated with AmberTools. I usually use it to add hydrogen atoms and modify ligands. This guide will be in the form a tutorial for setting up two glycogen phosphorylase (GP) ligands.

UCSF Chimera can be download from here

Samuel Genheden, 2012

The ligands

The complex is based on the 1FU4.pdb pdb-file. It contains another ligand than the two we will prepare. The two ligands that we will prepare look like this:

Preparatory steps - remove the surroundings

Open the pdb-file of the complex in Chimera by typing

chimera complex.pdb

it could be a prepared pdb-file or the raw pdb-file from the Internet.

We will start by removing all atoms except the ligand. First select the ligand by going to the Select -> Residue menu and click on GL9

The ligand will now be marked in green at the center of the screen.

Then, go to the Select menu and click on Invert selection. This will select everything but the ligand itself.

To remove the selected atom, goto Action -> Atoms/Bond menu and click on delete

Preparing the first ligand

Now, zoom in on the ligand and center it on the screen. This is how you control the atoms on the screen:

LinuxMac
ZoomRight mouse-buttonCmd+click
RotateLeft mouse-buttonClick
TranslateMiddle mouse-buttonAlt+click

Next, select the atoms that are marked in the picture below. Selecting is done by Ctrl+Click and to select more than one atom, Ctrl+Alt+Click.

The selected atoms are the atoms that do not exist in our ligands. So remove them by going to Actions -> Atoms/Bonds -> delete .

Now there is a nitrogen atom in the ligand where it should be a hydrogen. Therefore, we will change this atom into a hydrogen. First, select the nitrogen atom by Ctrl+Click.

Then go to Tools -> Structure Editing and click on Build structure

A new window will appear, go to the second page, Modify structure. The window will now look something like this:

Here, we can modify our atoms.

  1. Change the element to a hydrogen, and number of bonds to 1
  2. Change the name to H70. I always try to have big numbers on atoms that will be mutated in an FEP, so that they will be easily distinguished from the other atoms.
  3. Modify the residue name to L01
Now, the window should look something like this:

Click on the Apply-button to make the changes.

Now, we should add the other hydrogen atoms to the ligand. Because this is tedious to do by hand, we will let the program do it for us.

Go to Tools -> Structure Editing and click on AddH

A new window will appear, and just click on the OK-button.

Now our first ligand is prepared and it is time to save it. Go to the File> menu and click on Save PDB....

In the window that appears, save the structure as l01.pdb. Note: it is important to have the Use untransformed coordinates checkbox selected, otherwise the structure will not be in the complex reference frame.

Preparing the second ligand

Now we should prepare our second ligand, and we start this by changing the hydrogen to a nitrogen. Select the hydrogen and click on Tools -> Structure editing -> Build structure

  1. Change the element to nitrogen, the number of bonds to 3 and the geometry to triogonal
  2. Set the name to N70. I try to have the "same" number of the atoms that should be perturbed.
  3. Set the residue name to L02

Chimera automatically adds two hydrogens, but we should change the name of them.
Select one of the hydrogen atoms and change its name to N71

Select the second one and change its name to N72.

Now we have prepared the second ligand. Let save the structure by clicking on File -> Save PDB...