Hi Andrii Lesiuk

You are correct when you mentioned that "Hydrogens are being added to a receptor protein in order to fix it structure"

I'm also sure you realised that when preparing the protein using ADT, only the polar hydrogens remained on the protein where all of the non-polar hydrogens are merged (You can check the generated pdbqt file).

Therefore, the same goes for the ligand(s).

Only polar hydrogens are calculated in AutoDock4.

Hope this help. All the best.

Andrii Lesiuk

Hi

Before docking, ligand and protein preparation is a very important step. Minimize both structures to remove the geometry error from the ligand and protein so the hydrogen adds by applying force field by Discovery studio also apply the polar and non-polar hydrogen using the ADT.

Here are some considerations:

Docking Software: Different molecular docking software packages handle hydrogen atoms differently. Some software, like AutoDock, do not require users to add hydrogen atoms to the ligand, as they can predict hydrogen positions during the docking process. Others, like AutoDock Vina, rely on hydrogen atoms being present in the ligand.

Ligand Preparation: If your ligand structure lacks hydrogen atoms, some docking programs may not be able to accurately predict interactions involving hydrogen bonds. In such cases, you may need to add hydrogen atoms to the ligand using molecular editing software.

Research Goals: The decision to add hydrogen atoms to the ligand may also depend on your research goals. If you want to study hydrogen bonding interactions between the ligand and the receptor, it's essential to have accurate hydrogen positions.

Ligand Flexibility: If your ligand is flexible and can form hydrogen bonds with the receptor, accurate hydrogen positions become more critical. In rigid ligand docking, where ligands are considered to be unchanging, this may be less of a concern.

Hydrogen Bonding: Hydrogen bonds play a crucial role in molecular recognition. Accurate modeling of hydrogen bonds can significantly impact the quality of your docking results.