Problem in file (Broken structure ini.pdb) generated using CGenFF for proceeding in MD Simulation

User discussions
1

GROMACS version: 5.1
GROMACS modification: Yes/No

Sir,

I am running protein-ligand complex md simulation by Gromacs 5.1 and I am encountering a problem in Ligand topology when I submit fix.mol2 file(generated by perl sort_mol2_bonds.pl F3871.mol2 F3871_fix.mol2) in CGenFF, .str file is ​generated but when I run next command (python cgenff_charmm2gmx_py3_nx2.py F3871 F3871_fix.mol2 F3871.str charmm36-feb2021.ff), as a result .ini.pdb file that is generated contains broken structure.
If I proceed with same broken file, I get the following errors in generation of .tpr file after running command
gmx grompp -f ions.mdp -c solv.gro -p topol.top -o ions.tpr
ERROR 1 [file f3871.itp, line 513]:
No default U-B types

8 10 20 5 ; CG2O1 NG2S0 CG2R61
ERROR 2 [file f3871.itp, line 724]:
No default Proper Dih. types
7 8 10 20 9 ; CG321 CG2O1 NG2S0 CG2R61
ERROR 3 [file f3871.itp, line 726]:
No default Proper Dih. types
9 8 10 20 9 ; OG2D1 CG2O1 NG2S0 CG2R61
ERROR 4 [file f3871.itp, line 733]:
No default Proper Dih. types
8 10 20 15 9 ; CG2O1 NG2S0 CG2R61 CG2R61

ERROR 5 [file f3871.itp, line 734]:
No default Proper Dih. types
8 10 20 19 9 ; CG2O1 NG2S0 CG2R61 CG2R61

Please help me in this regard as I am stuck in this problem and unable to proceed further. How can I resolve this issue?

Thanking you in anticipation.

2

Did the conversion script generate a .prm file, and did you #include it in your topology before the ligand definition? Any missing parameters should be there, though the CGenFF server now provides a much newer version of the force field than what is available in our port, thus the missing parameters may actually be standard in the force field and are not generated as new for each molecule. A new port will be available soon that should resolve this.

Regarding the “broken” structure - can you provide an image? Does the residue name of your molecule fit within 4 characters, thus not violating PDB standards? The conversion script isn’t always very intelligent, but I thought we had resolved this long ago to only write 4 characters and thus avoid shifting the coordinate columns.

3

I have attached the broken structure seen in f3871.ini.pdb

image
image847×650 87.8 KB

Yes it generated a .prm file also and I have included #include it in topology before the ligand definition as mentioned in tutorial.
Molecule name is F3871 in my study,
As per your suggestion, I have changed it to F38 and started the process again from the start, in this case f38.ini.pdb file structure remained intact as shown in 2nd image but while adding ions step in generation of ions.tpr file by command (gmx grompp -f ions.mdp -c solv.gro -p topol.top -o ions.tpr)
the same errors appear
Command line:
gmx grompp -f ions.mdp -c solv.gro -p topol.top -o ions.tpr

Ignoring obsolete mdp entry ‘title’

Back Off! I just backed up mdout.mdp to ./#mdout.mdp.1#

NOTE 1 [file ions.mdp]:
With Verlet lists the optimal nstlist is >= 10, with GPUs >= 20. Note
that with the Verlet scheme, nstlist has no effect on the accuracy of
your simulation.

Setting the LD random seed to 1950987229
Generated 100465 of the 100576 non-bonded parameter combinations
Generating 1-4 interactions: fudge = 1
Generated 66298 of the 100576 1-4 parameter combinations

ERROR 1 [file f38.itp, line 513]:
No default U-B types

ERROR 2 [file f38.itp, line 724]:
No default Proper Dih. types

ERROR 3 [file f38.itp, line 726]:
No default Proper Dih. types

ERROR 4 [file f38.itp, line 733]:
No default Proper Dih. types

ERROR 5 [file f38.itp, line 734]:
No default Proper Dih. types

Excluding 3 bonded neighbours molecule type ‘Protein_chain_A’
Excluding 3 bonded neighbours molecule type ‘F38’
Excluding 2 bonded neighbours molecule type ‘SOL’

NOTE 2 [file topol.top, line 53006]:
System has non-zero total charge: 4.000004
Total charge should normally be an integer. See
GROMACS - Gromacs
for discussion on how close it should be to an integer.

Removing all charge groups because cutoff-scheme=Verlet

There were 2 notes

Program gmx grompp, VERSION 5.1
Source code file: /share/apps/packages/gromacs/gromacs-5.1/src/gromacs/gmxpreprocess/grompp.c, line: 1738

Fatal error:
There were 5 errors in input file(s)

What can be the reason behind it? Please help me in resolving this problem as I am stuck in it and unable to run it further.

4

The missing parameters are due to the need for the newer force field. I am working on it but it won’t be publicly available for a little while longer as I need to run it through a battery of tests before I let anyone else use it.

5

Sir please let me know whenever you update it as my work is totally stuck due to these 5 errors in md simulation of my ligands.

6

Hi @jalemkul. In my case, the molecule appears fine until the bonds are sorted usi g the perl script. Something goes wrong at when I upload it to CGenFF and the ligand is fragmented. Any clue as to what might be going wrong?

image

7

Your residue name is longer than 4 characters so it breaks the PDB format. Shorten the residue name and run the conversion again.

1 Like
8

Yessssss. I just figured that out after having a proper look at the ‘cgenff_charmm2gmx_py3_nx2.py.’ 😭Wasted hours implementing this solution molecular dynamics - Alternative to CGenFF for generating large ligand topology - Matter Modeling Stack Exchange