Forecfield incorporation in gromacs

User discussions
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1

GROMACS version:2018
GROMACS modification: Yes/No
Hello all ,
I am running a simulation for protein membrane system . I added the ligand molecule to the system , for which I created the forcefiled parameters in antechamber . I am using the charmm36 forcefield for the membrane protein system . Then I added the forcefiled of the molecule as .itp file and modified the topology.top file of the system . But when I am ruuning the simulation , the minimization goes well , but when the nvt equillibration starts , I am getting the error and creation of many new .pdb files Too many LINCS warnings (1006)
If you know what you are doing you can adjust the lincs warning threshold in
your mdp file
or set the environment variable GMX_MAXCONSTRWARN to -1,
but normally it is better to fix the problem
" . Can you please check , if I have incorporated the .itp file correctly and modified the topology.top file in the right manner .
topol.top (1.2 KB)
and my .itp file of the molecule looks like this ,
; UNL_GMX.top created by acpype (v: 2022.7.21) on Thu Mar 28 22:16:28 2024

[ moleculetype ]
;name nrexcl
UNL 3

[ atoms ]
; nr type resi res atom cgnr charge mass ; qtot bond_type
1 CT 1 UNL C 1 -0.100000 12.01000 ; qtot -0.100
2 HC 1 UNL H1 2 0.076700 1.00800 ; qtot -0.023
3 HC 1 UNL H2 3 0.076700 1.00800 ; qtot 0.053
4 HC 1 UNL H3 4 0.076700 1.00800 ; qtot 0.130
5 As 1 UNL AS 5 0.141500 74.92000 ; qtot 0.272
6 OH 1 UNL O1 6 -0.541400 16.00000 ; qtot -0.270
7 HO 1 UNL H4 7 0.405600 1.00800 ; qtot 0.136
8 OH 1 UNL O 8 -0.541400 16.00000 ; qtot -0.406
9 HO 1 UNL H 9 0.405600 1.00800 ; qtot 0.000

[ bonds ]
; ai aj funct r k
1 2 1 1.0900e-01 2.8451e+05 ; C - H1
1 3 1 1.0900e-01 2.8451e+05 ; C - H2
1 4 1 1.0900e-01 2.8451e+05 ; C - H3
1 5 1 1.5100e-01 2.7196e+05 ; C - AS
5 6 1 1.3390e-01 3.5146e+05 ; AS - O1
5 8 1 1.3390e-01 3.5146e+05 ; AS - O
6 7 1 9.6000e-02 4.6442e+05 ; O1 - H4
8 9 1 9.6000e-02 4.6442e+05 ; O - H

[ pairs ]
; ai aj funct
1 7 1 ; C - H4
1 9 1 ; C - H
2 6 1 ; H1 - O1
2 8 1 ; H1 - O
3 6 1 ; H2 - O1
3 8 1 ; H2 - O
4 6 1 ; H3 - O1
4 8 1 ; H3 - O
6 9 1 ; O1 - H
7 8 1 ; H4 - O

[ angles ]
; ai aj ak funct theta cth
1 5 6 1 1.1516e+02 5.8576e+02 ; C - AS - O1
1 5 8 1 1.1516e+02 5.8576e+02 ; C - AS - O
2 1 3 1 1.0950e+02 2.9288e+02 ; H1 - C - H2
2 1 4 1 1.0950e+02 2.9288e+02 ; H1 - C - H3
2 1 5 1 1.1036e+02 3.7656e+02 ; H1 - C - AS
3 1 4 1 1.0950e+02 2.9288e+02 ; H2 - C - H3
3 1 5 1 1.1036e+02 3.7656e+02 ; H2 - C - AS
4 1 5 1 1.1036e+02 3.7656e+02 ; H3 - C - AS
5 6 7 1 1.0763e+02 4.1840e+02 ; AS - O1 - H4
5 8 9 1 1.0763e+02 4.1840e+02 ; AS - O - H
6 5 8 1 1.1433e+02 6.2760e+02 ; O1 - AS - O

[ dihedrals ] ; propers
; for gromacs 4.5 or higher, using funct 9
; i j k l func phase kd pn
1 5 6 7 9 180.00 4.39320 2 ; C- AS- O1- H4
1 5 8 9 9 180.00 4.39320 2 ; C- AS- O- H
2 1 5 6 9 0.00 0.00000 0 ; H1- C- AS- O1
2 1 5 8 9 0.00 0.00000 0 ; H1- C- AS- O
3 1 5 6 9 0.00 0.00000 0 ; H2- C- AS- O1
3 1 5 8 9 0.00 0.00000 0 ; H2- C- AS- O
4 1 5 6 9 0.00 0.00000 0 ; H3- C- AS- O1
4 1 5 8 9 0.00 0.00000 0 ; H3- C- AS- O
6 5 8 9 9 180.00 4.39320 2 ; O1- AS- O- H
7 6 5 8 9 180.00 4.39320 2 ; H4- O1- AS- O

#ifdef AR_mol
[ position_restraints ]
1 1 AR_mol AR_mol AR_mol
5 1 AR_mol AR_mol AR_mol
6 1 AR_mol AR_mol AR_mol
8 1 AR_mol AR_mol AR_mol

#endif

2

It is most likely that the incorporation of the topology is wrong then you wouldn’t be able to compile any .tpr files, so I guess that isn’t the problem. Regarding the topology itself, I don’t have enough experience to comment by eye.

However, typically LINCS warnings are related to bad starting structures. Have you checked which atoms are giving you LINCS problems? Are they clashing with other atoms? The energy minimization went through, but it can still be a bad starting structure. Also, if all the warnings come from the new parametrized molecule than it is also likely that it can be a parametrization problem.

3

I checked with the structure and energy minimization goes well and I am not sure whether I have correctly incorporated the ligand forcefield parameters in the .top and .itp file .

4

Dear Sir,
I have a one doubt. While create force field by using antechamber did you modified charge in mol2 file by RESP charge fitting.

Best Regards,
LUKHMANUL HAKEEM K.

5

Which forcefiled you used for ligand ? @maajid

6

I incorporated the ligand in charmm36 forcefield in gromacs

7

There is something wrong with your simulation system, check the output shows when you run on the nvt.
Probabaly issue is with your ligand paramter, btw, why your ligand charges are zero?

8

Before you proceed too far you should also carefully consider if the parameters you generate with antechamber are compatible with charmm36. I.e., when you get past any technical problems and you get the simulation to start, will the results make any sense at all?

9

Thank you Magnusl . Is it more feasible if I use amber forcefield for whole sysytem in place of charmm36 as my ligand ff is amber compatible ?

10

Yes, I would definitely suggest using an amber force field for the rest of the system if you generate the ligand parameters using antechamber. If you want to use a charmm36 force field for the protein and lipids I would suggest using CGenFF (or possibly MATCH) to generate the ligand parameters. Mixing force fields are not a good idea, unless you really know what you are doing.

11

Thank you @MagnusL for your valuable suggestion.