Inconsistent shifts over periodic boundaries, a problem with the ligand

[nvphuoc1105]

GROMACS version: 2026.0-dev-20241213-9ac17bb403
GROMACS modification: Yes/No
Dear friends,

Currently, I am working with MD Simulation with GROMACS 2023 and everything has been going well. Except this one:

When I try the energy minimization with the below commands, such an error occurred

• gmx grompp -f em.mdp -c solv_ions.gro -p topol.top -o em.tpr

• gmx mdrun -v -deffnm em

I tried to increase the box size with the command:

• gmx editconf -f complex.gro -o newbox.gro -bt dodecahedron -d 1.4

But even when I set “-d 10.0”, the problem still exists with other residues belong to the ligand so I believe there is a systematic problem with the ligand.
Also, if I set “-d 10.0” and change the rlist = rcoulomb = rvdw = 13 in the em.mdp file. It can run but still
“Steepest Descents:
Tolerance (Fmax) = 1.00000e+03
Number of steps = 500000
Killed”

I used CGENFF to generate the “Ligand.str file”. It works well in other cases (protein in complex with or without ligand". Also, I view the complex structure with Pymol and Discovery Studio 2021 but do not realize any abnormal sign of the complex, or it is because I do not know how to view correctly to identify errors.

So I am begging for your help, any help is appreciated.

Thank you and best regards.

[hess]

My guess is that a molecule is broken over periodic boundaries in your initial structure. Did you look at the coordinates of atoms 1874 and 1900 in your structure file before increasing the box size?

[nvphuoc1105]

Dear hess,
Thank you so much for your reply.

As all the residues related to this kind of error are Ligand’s residue, and I believe there was a problem with my Ligand files as it is broken when I combined the protein topology file and the ligand topology file.

The pictures below are my: Ligand.gro, solv.gro, and solv_ions.gro, respectively.

Can you recognize any abnormalities and how to do it?

Looking forward to hearing from you.
Thank you!

[hess]

If H20 is bonded to C23, then there is an issue in either your input coordinates or in the ordering of the coordinates.

[nvphuoc1105]

Dear hess,
The MD Simulation is running now and I did not face any problems throughout the whole process.
I want to share my procedure so I can hear your advice,
After using Open Babel to add Hydrogens (make explicit) and get the mol2.file
I run this script to fix the mol2.file:

• perl sort_mol2_bonds.pl Ligand.mol2 Ligand.mol2
  Then I slightly adjust the Ligand_fix.mol2 file
  
  
• The point is the Ligand_fix.mol2 file and names in red, if I keep the name “Ligand” then run CGENFF to obtain the ligand_ini.pdb file, the molecules will be broken
  
  
  
  However if I modify the name “Ligand” to some random name like “dcm”, the molecule is normal.
  
  
  
  As I am an amateur in this field, can you illustrate the reason for this phenomenon.
  In addition, for the nvt.mdp and npt.mdp file, I keep pcoupl = C-rescale in the section “Pressure coupling” recommendation from GROMACS but the pressure coupling in the md.mdp file is Parrinello-Rahman and it still run normally without any Warning, then how does this affect the result?

Thank you so much for your prestigious advice.

[jalemkul]

@nvphuoc1105

However if I modify the name “Ligand” to some random name like “dcm”, the molecule is normal.

PDB files only permit a maximum of 4 characters in the residue name. Anything longer will result in the coordinate fields being shifted and therefore incorrectly interpreted. I thought we had fixed this in the conversion script but apparently not.