Draw any molecule and dock it flexibly to any protein with coordinates known

Wouldn't it be great to be able to draw any molecule you can imagine and dock it flexibly to a protein of your choice from the PDB
database?

Can be done.

Step 1: draw a molecule, convert it to 3D and save as *.MOL

To draw a chemical structure, you can use ChemSketch program.

Manual drawing of a molecule from scratch in ChemSketch

3D conversion in ChemSketch

Step 2: convert *.MOL to *.PDB

Open Babel, PyMOL or our conversion tools can be used to convert the *.MOL file to *.PDB.

Step 3: prepare PDBQT of the ligand and the protein

Use MGLTools or our conversion utility to prepare PDBQT files from the PDB files of your above ligand and protein target of your choice from the PDB data bank.

Step 4: dock the small molecule to your protein

For this step you can use VcPpt. Drag and Drop the protein and ligand PDBQT files and click RUN.

The protein of choice this time will be HIV reverse transcriptase, PDB ID 3MEC.

Once the docking is complete, it seems that this small molecule does not bind very strongly. A score of -9 to -12 would be expacted for a well-binding ligand. How about adding a few carbon atoms ?

Still not great, but definitely better. Let's look where it bound and how.

HIV reverse transcriptase complex with docked ligand

Real structure with co-crystallized                                                     Docking prediction with the example
ligand (shown for reference)                                                              drug just drawn in ChemSketch - note that
                                                                                                              the molecule was docked in the same pocket
                                                                                                              without any prior knowledge