How to generate a MOL2 ligand file with the correct docking pose, full hydrogens, and physiological

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GROMACS version: 2026.2
GROMACS modification: No
Hello everyone,

I am currently preparing a molecular dynamics simulation for a protein–ligand complex. The ligand pose was obtained from molecular docking using AutoDock Vina, and the coordinates of the ligand in the binding pocket seem to be correct.

However, I have encountered a problem during ligand preparation for MD. The ligand file extracted from the docking pose is in PDB/PDBQT format, but the atom names are very generic, for example C, C, C, O, O, instead of unique names such as C1, C2, C3, O1, O2, O3. In addition, the ligand does not contain all hydrogens because the non-polar hydrogens were merged during docking preparation.

I would like to run the MD simulation under physiological conditions, around pH 7.4. Therefore, I need to generate a MOL2 file that satisfies the following conditions:

  1. It preserves the correct docking pose/conformation obtained from AutoDock Vina.
  2. It contains all hydrogens, including non-polar hydrogens.
  3. It has the correct protonation state at physiological pH.
  4. It has atom names that are consistent with the topology files used in GROMACS.

I also have the original MOL2 file of the ligand with the correct chemical structure. I used this MOL2 file to generate the ligand parameter files, including the .str and .itp files. However, when I try to merge the ligand with the receptor to build the complex in GROMACS, I get an error indicating that the number of hydrogen atoms does not match. On the other hand, if I use the ini.pdb file generated during the topology preparation, the ligand no longer has the correct docking pose.

Could anyone suggest a proper workflow to generate a ligand MOL2/PDB file that keeps the docking pose but also has the correct full-hydrogen structure and matches the generated topology?

Any advice would be greatly appreciated.

Thank you very much.