Converting the target molecule into PDBQT

Molecule conversions are a crucial point of AutoDock computations. AutoDock uses PDB format as its base but it cannot make calculations with PDB. AutoDock needs to convert PDB files into PDBQT files. Thankfully it comes with a free AutoDockTools app and if you are lucky, it is easy to make conversions. AutoDock package could drive you crazy while you are trying to make conversions or create configuration files but there are not any other options.

As I said, the app we need to use is AutoDockTools and it is a part of MGLTools  (Molecular Graphics Laboratory Tools) software. Download and install it. Even though I usually work on Mac and Linux I was not able to install MGLTools into any of my UNIX based (Mac or Linux) machines. Mostly the Python version is the problem. MGLTools requires an archaic version of the Python Programming Language. UNIX based systems generally use Python extensively so it is hard to change the system default for MGLTools.

I started my Windows machine and install the Windows version. Installation is pretty straightforward. Just click Next, Next, Next and it is ready to use. The installation wizard will start Python Molecule Viewer at the end but you do not need that. You have to start AutoDockTools via Start menu or the Desktop icon.

After launching the app, you can directly try to open your PDB molecule. File > Read Molecule.

The molecule will be visible on the main window. Edit > Charges > Compute Gasteiger

The resulting warning may be discouraging. But do not worry.

Just click OK and continue with; Grid > Macromolecule > Choose

You will be prompt with the next screen:

Pay attention to the saving address. You have to write the full address of the path including the filename and the extension.

In the end, if you have not experienced any other error you will have a new pdbqt file of your macromolecule.

NEXT: Converting the ligand molecule into PDBQT

Obtaining a Ligand Structure

Sometimes you do not have to create your prospective lead molecule (first ligand molecule to start). In our example, one of the ligand molecules is already in the PDB molecule. It was crystalized while safinamide molecule and we can get it from PDB file.

In the beginning, the strategy of the experiment could be seen a little odd. We are getting a ligand structure form an already docked complex and trying to dock again into the same target! The result should be obvious, right? Yes, that is correct but while we are searching for a new molecule the known lead molecule will help us to find novel therapeutics. Actually, that is why we call it lead molecule.

We will separate the safinamide from MAO-B and re-dock them with a docking tool. While doing that we will be sure about our experiment process. After that make small changes to the lead molecule and invent brand new ligands. After that, the testing (the docking) process will come in handy.

When I review the downloaded target molecule I can see the extra section of atoms. This part is generally indicated with HTATM type. But be careful. FAD is also indicated similarly and it is part of MAO-B. Is it even the binding part of MAO-B. At this point, you have to have some general idea about this target molecule. You can find the reference article which is authored by the scientists who make the crystallography.

Get the safinamide part and save it as ligand.pdb. In the next sections we will concert it into PDBQT format.

NEXT: Converting the target molecule into PDBQT.