Protein-Ligand MMPBSA calculations challenges

francis acquah466

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Mar 20, 2021, 10:19:59 PM3/20/21

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Dear gmx_MMPBSA users,

Please I have a small challenge. I have tried running gmx_MMPBSA and failed. I installed as stated on GitHub.

The examples on GitHub run very well.

However when I run on my examples, I get the following error.

==============================================

(base) [francis@dhcp-10-64-14-120 Lemkul-ProLigCom]$ gmx_MMPBSA -O -i mmpbsa.in -cs md_0_10.tpr -ci index.ndx -cg 1 13 -ct md_0_10.xtc -lm jz4_fix.mol2
[INFO   ] Started
[INFO   ] Loading and checking parameter files for compatibility...

[INFO   ] Checking external programs...
[INFO   ] cpptraj found! Using /opt/amber20/bin/cpptraj
[INFO   ] tleap found! Using /opt/amber20/bin/tleap
[INFO   ] parmchk2 found! Using /opt/amber20/bin/parmchk2
[INFO   ] mmpbsa_py_energy found! Using /opt/amber20/bin/mmpbsa_py_energy
[INFO   ] Using GROMACS version > 5.x.x!
[INFO   ] gmx found! Using /usr/local/gromacs/bin/gmx
[INFO   ] Checking external programs...Done.

[INFO   ] Building AMBER Topologies from GROMACS files...
[INFO   ] Checking if supported force fields exists in Amber data...
[INFO   ] Get PDB files from GROMACS structures files...
[INFO   ] Making gmx_MMPBSA index for complex...
[INFO   ] Normal Complex: Saving group 1_13 in _GMXMMPBSA_COM_index.ndx file as _GMXMMPBSA_COM.pdb
[INFO   ] Generating ligand parameters from jz4_fix.mol2 file...
[ERROR ] /opt/amber20/bin/parmchk2 failed when querying jz4_fix.mol2
File "/opt/amber20/miniconda/bin/gmx_MMPBSA", line 8, in <module>
    sys.exit(gmxmmpbsa())
File "/opt/amber20/miniconda/lib/python3.8/site-packages/GMXMMPBSA/app.py", line 111, in gmxmmpbsa
    app.loadcheck_prmtops()
File "/opt/amber20/miniconda/lib/python3.8/site-packages/GMXMMPBSA/main.py", line 588, in loadcheck_prmtops
    FILES.mutant_receptor_prmtop, FILES.mutant_ligand_prmtop) = maketop.buildTopology()
File "/opt/amber20/miniconda/lib/python3.8/site-packages/GMXMMPBSA/make_top.py", line 116, in buildTopology
    self.gmx2pdb()
File "/opt/amber20/miniconda/lib/python3.8/site-packages/GMXMMPBSA/make_top.py", line 188, in gmx2pdb
    GMXMMPBSA_ERROR('%s failed when querying %s' % (parmchk2, self.FILES.ligand_mol2))
File "/opt/amber20/miniconda/lib/python3.8/site-packages/GMXMMPBSA/exceptions.py", line 170, in __init__
    raise exc(msg + ' Check the gmx_MMPBSA.log file to report the problem.')
MMPBSA_Error: /opt/amber20/bin/parmchk2 failed when querying jz4_fix.mol2 Check the gmx_MMPBSA.log file to report the problem.
Exiting. All files have been retained.

=================================================================

I will appreciate all the help I can get !!!!

Thanks

Francis

Mario Sergio Valdes

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Mar 20, 2021, 10:24:18 PM3/20/21

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Welcome!

Is that mol2 file the output of antechamber?

francis acquah466

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Mar 20, 2021, 10:31:48 PM3/20/21

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Thanks for the swift response.

No it is not.

The jz4_fix.mol2 is actually from avogadro software.

Do I have to generate the ligand mol2 file in antechamber?

Francis.

Mario Sergio Valdes

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Mar 20, 2021, 10:42:33 PM3/20/21

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Yes. In this case, you must define exactly the same mol2 file as the ligand parameterization. In very rare cases, you can regenerate the ligand mol2 file with Antechamber (it can generate inconsistencies) using the structure of the ligand extracted from the tpr file. If you want to use the topology instead of the structure you would not have to define the ligand mol2 file (you can refer to this https://valdes-tresanco-ms.github.io/gmx_MMPBSA/examples/Protein_ligand_CHARMMff/, it applies exactly the same for the Amber force field). The CHARMM force field is only supported using topology, while the Amber force field is supported by both topology and structure.

francis acquah466

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Mar 21, 2021, 8:11:52 PM3/21/21

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Hi Mario,

Thank you for the link showing the ChARMM force field option. It worked for my example above.

My challenge now is that when I adopt it to other complexes I have I get this error::

==============================================

(base) [francis@dhcp-10-64-14-120 lig108020OKK]$ gmx_MMPBSA -O -i mmpbsa.in -cs md_0_50.tpr -ci index.ndx -cg 1 13 -ct md_0_50.xtc -cp topol.top

[INFO   ] Started
[INFO   ] Loading and checking parameter files for compatibility...

[INFO   ] Checking external programs...
[INFO   ] cpptraj found! Using /opt/amber20/bin/cpptraj
[INFO   ] tleap found! Using /opt/amber20/bin/tleap
[INFO   ] parmchk2 found! Using /opt/amber20/bin/parmchk2

[INFO ] sander found! Using /opt/amber20/bin/sander

[INFO   ] Using GROMACS version > 5.x.x!
[INFO   ] gmx found! Using /usr/local/gromacs/bin/gmx
[INFO   ] Checking external programs...Done.

[INFO   ] Building AMBER Topologies from GROMACS files...
[INFO   ] Checking if supported force fields exists in Amber data...
[INFO   ] Get PDB files from GROMACS structures files...
[INFO   ] Making gmx_MMPBSA index for complex...
[INFO   ] Normal Complex: Saving group 1_13 in _GMXMMPBSA_COM_index.ndx file as _GMXMMPBSA_COM.pdb

[INFO   ] No receptor structure file was defined. Using ST approach...
[INFO   ] Using receptor structure from complex to generate AMBER topology
[INFO   ] Normal Complex: Saving group 1 in _GMXMMPBSA_COM_index.ndx file as _GMXMMPBSA_REC.pdb
[INFO   ] No ligand structure file was defined. Using ST approach...
[INFO   ] Using ligand structure from complex to generate AMBER topology
[INFO   ] Normal ligand: Saving group 13 in _GMXMMPBSA_COM_index.ndx file as _GMXMMPBSA_LIG.pdb
[INFO   ] Cleaning GROMACS topologies...
[INFO   ] Building Normal Complex Amber Topology...

File "/opt/amber20/miniconda/bin/gmx_MMPBSA", line 8, in <module>
    sys.exit(gmxmmpbsa())
File "/opt/amber20/miniconda/lib/python3.8/site-packages/GMXMMPBSA/app.py", line 111, in gmxmmpbsa
    app.loadcheck_prmtops()
File "/opt/amber20/miniconda/lib/python3.8/site-packages/GMXMMPBSA/main.py", line 588, in loadcheck_prmtops
    FILES.mutant_receptor_prmtop, FILES.mutant_ligand_prmtop) = maketop.buildTopology()

File "/opt/amber20/miniconda/lib/python3.8/site-packages/GMXMMPBSA/make_top.py", line 124, in buildTopology
    tops = self.gmxtop2prmtop()
File "/opt/amber20/miniconda/lib/python3.8/site-packages/GMXMMPBSA/make_top.py", line 294, in gmxtop2prmtop
    com_top = parmed.gromacs.GromacsTopologyFile(self.complex_temp_top, xyz=self.complex_str_file)
File "/opt/amber20/lib/python3.8/site-packages/parmed/gromacs/gromacstop.py", line 259, in __init__
    self.coordinates = f.coordinates
File "/opt/amber20/lib/python3.8/site-packages/parmed/structure.py", line 1700, in coordinates
    coords = coords.reshape((-1, len(self.atoms), 3))
ValueError: cannot reshape array of size 338451 into shape (2070,3)

Exiting. All files have been retained.

===========================================================

Is there a flag I am missing.??

Mario Sergio Valdes

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Mar 21, 2021, 8:15:26 PM3/21/21

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Hi Francis.

It is probably due to a mismatch between the topology and the structure. Can you send me the files to review?

Best!

francis acquah466

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Mar 21, 2021, 8:39:09 PM3/21/21

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Mario,

I shared the files including the trajectory file with you via google drive due to the size.

Regards
Francis

Mario Sergio Valdes

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Mar 21, 2021, 8:41:13 PM3/21/21

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I will try to solve it as soon as possible.

Mario Sergio Valdes

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Mar 23, 2021, 11:55:00 AM3/23/21

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Dear Francis.

Did you solve the doubts?

Mario S

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