The pretreatment of receptor proteins by autodock and smina is different?

[Anna Cooper]

Hello! I am a novice in molecular docking and have some confusion. Why is the receptor.pdbqt file(that downloads from PDB then removes ligands and charges by autodock) prepared for docking, different from the receptor.pdbqt obtained from (python) smina processing? Many Thanks!

[David Koes]

It isn't clear to me what your workflow is, but smina uses OpenBabel to construct its PDBQT, not autodock tools.

[Anna Cooper]

Thanks, a tutorial from the web was used for my workflow: prepare protein and ligand, define the binding site, and finally dock. But that directly converts receptor(.pdb) file to pdbqt file without separating them, and I also find a few amino acid residues are lost in this progress, does that matter in the final results?

[Tao]

Hi, would you mind providing the link to the script you posted? In order to answer the questions we discussed, I would like to have a look at it.

[David Koes]

I'm sorry, I'm not sure what you are asking. If you provide a pdbqt, smina will use it exactly as-is. If you provide a pdb, openbabel will be used to convert it to an pdbqt internally.

[Tao]

Dear Koes,

I can understand what him/her was asking. Because I have the same question recently when I try to do structure-based virtual screening using smina.

In the tutorial, smina runs with receptor.pdb and combined_ligand.sdf. The problem is autodock4 would prefer using pdbqt format input for it is protonated and added hydrogen. In addition, some believe that protonated ligands and receptors could dock more precisely and results could be more confident.

Our questions are:

1. Does smina run with unprotonated ligands and receptors?
2. Will this (if running without protonating and adding hydrogen ) affect the accuracy of docking?
3. Do we need to protonate the receptor and ligand before running smina?

If you could please answer these questions, I would greatly appreciate it.

[David Koes]

If you provide a pdbqt, smina will use it exactly as-is. If the pdbqt isn't protonated, then atom typing will be done without hydrogens. Any other file format and openbabel will be used to add hydrogens before performing atom typing.

Different atom typing from different protonation states will result in different docking scores.

[Tao]

Thank you so much for taking the time to answer our questions.