Druggability simulations assess the druggability of protein targets using molecular dynamics simulations in the presence of small probe molecules. In most ways, these are typical MD simulations, but their setup, owing to the inclusion of a diverse array of probe molecules, may be tricky. DruGUI 2.0 makes this process much easier by providing a convenient GUI with which users can set up druggability simulations which can then be run normally with NAMD. In this example, we show how to prepare and analyze a druggability simulation using The DruGUI 2.0 interface. As an example, we will use chain A of the protein murine double minute 2 homolog MDM2 (PDB:**1YCR) and prepare the structure for druggability simulation.

Required Programs¶

The latest development version of ProDy from GitHub is required, as well as a working VMD installation. Head over to GitHub and follow the installation instructions there for ProDy: https://github.com/prody/ProDy/blob/main/INSTALL.rst#installing-from-source-not-recommended. VMD can be downloaded for free from this link after registering: https://www.ks.uiuc.edu/Development/Download/download.cgi?PackageName=VMD.

Getting Started¶

  • Install VMD (https://www.ks.uiuc.edu/Development/Download/download.cgi?PackageName=VMD) and copy the path to its executable. For Linux-based machines, this is usually /usr/bin/local/vmd, but this may be different on MacOS, so check before beginning.
  • Install ProDy from source (see Introduction for more details).
  • Prepare two files for your protein, 1) a Protein Strucure File (PSF) and 2) a Protein Data Bank (PDB) structure file. In the included tutorial files we provide these two files for MDM2 (mdm2.psf and mdm2.pdb). VMD can be used to generate PSF and PDB files (please see this VMD tutorial on how to do that: https://www.ks.uiuc.edu/Training/Tutorials/vmd/tutorial-html/).
  • Download CHARMM forcefield topology and parameter files to prepare the MD simulations. These files can be obtained from this webpage: https://mackerell.umaryland.edu/charmm_ff.shtml. Extract these files and keep them in the folder where your PSF and PDB files are located, you will need to tell DruGUI where they are so that DruGUI can properly prepare your NAMD simulations. If your system has lipids or carbohydrates, make sure you have the appropriate files for those.

From within a Python session, run the following to import all ProDy modules and load up the DruGUI 2.0 window.

from prody import *
DruGUI()

After running the above code, you the DruGUI window will appear. Move to the next section to learn more about navigating this window.

How to Cite¶

If you benefited from DruGUI 2.0 in your research, please cite the following paper:

Bakan A, Nevins N, Lakdawala AS, Bahar I, Druggability Assessment of Allosteric Proteins by Dynamics Simulations in the Presence of Probe Molecules J Chem Theory Comput 2012, 8(7) :2435-2447. PMCID: PMC3392909