Hi,
I am new to GROMACS and recently try to run MD to find out the interaction between two small organic molecules. First I prepared the structures and simulate the protonation state under pH 7.
Then, the two molecules were docked to find the minimized docking position. I would like to use MD to check the behavior and binding affinity (potential energy) of two molecules with GROMACS.
However, with GROMACS, the force field is built for proteins... Therefore, I follow the guide in GORMACS tutorial to build the topology files with SwissParam. I took out mol.itp and mol.pdb and created a mol.top with the guide from https://www.researchgate.net/post/How_to_generate_top_file_for_Gromacs.
The top file that I modified is stated below.
#################################
; include forcefield parameters
# include "charmm27.ff/forcefield.itp"
; include drug topologies
# include "1.itp"
; include water topology
# include "charmm27.ff/spc.itp"
# ifdef POSRES_WATER
; Position restraint for each water oxygen
[ position_restraints ]
; i funct fcx fcy fcz
1 1 1000 1000 1000
#endif
; include topology for ions
# include "charmm27.ff/ions.itp"
[ system ]
; Name
System
[ molecules ]
; Compound #mols
LIG 1
SOL 2605
#########################################
After getting the files (.pdb, .itp, .top), I ran the command to generate box.
gmx editconf -f 1.pdb -o 1.gro -bt cubic -c -d 1.5
And..
gmx solvate -cp 1.gro -cs spc216.gro -o 1_water.gro -p 1.top
to solvate the system in water model.
Next, I tried to add ions into the system. So I ran... (ions.mdp was taken from GROMACS tutorial)
gmx grompp -f ions.mdp -c 1_water.gro -p 1.top -o ions.tpr
I got the following error:
GROMACS: gmx grompp, version 2021.3
Executable: /usr/local/gromacs/bin/gmx
Data prefix: /usr/local/gromacs
Working dir: /mnt/d/md/PE
Command line:
gmx grompp -f ions.mdp -c 1_water.gro -p 1.top -o ions.tpr
Ignoring obsolete mdp entry 'ns_type'
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 -67372817
Generated 22791 of the 22791 non-bonded parameter combinations
Generating 1-4 interactions: fudge = 1
Generated 19663 of the 22791 1-4 parameter combinations
ERROR 1 [file 1.top, line 26]:
No such moleculetype DRG
There was 1 note
-------------------------------------------------------
Program: gmx grompp, version 2021.3
Source file: src/gromacs/gmxpreprocess/toppush.cpp (line 2512)
Fatal error:
There was 1 error in input file(s)
For more information and tips for troubleshooting, please check the GROMACS
website at http://www.gromacs.org/Documentation/Errors
-------------------------------------------------------
Could you help me to solve the problem? Or do you have any suggestion on how to simulate 2 small molecules?
Additionally, I would like to know how to add NaCl at 0.15 M. I could make neutral system by adding 1 Cl-...
Thank you very much!
Hi,
the error is in the text you posted here: in the topol.top you have a "LIG" but no "DRG", and on "ions.mdp" you have a "DRG" but no "LIG". You should add each topology to the topol.top
the DRG are loss in your 1.top, you can inculde it and make sure the molecule type in your itp file is DRG. Moreover, charmm 27 forcefield is too old for most cases, youd better update it to charmm 36
Ricardo J Ferreira and Nian Binbin Thank you very much for your answers.
After I include DRG in the top files, it worked.
Now, I have prepared the files and ready for MD production.
With the current settings, my MD simulation showed that the two small molecules eventually falling apart from the docked pose. Dose this means the weak forces between two molecules is not enough to hold them together?
Another thing is that I found that my small molecules in the pdb that I downloaded from the SwissParam is missing some part of my original structure.
In the original pdb I have R-C=O. But, in the files from SwissParam became R-C-O.
I am losing the double bond between C and O. Additionally, I also found that the double bonds between P and O are missing too and some charges were also different.
Do you have any suggestion on how to properly prepare the topology file for simulation on the interaction of two small organic molecules in GROMACS or maybe in other program (ex. AMBER)? On the other hand, could you give me some advice on choosing proper force filed for simulation?
Finally, I would like to simulate the interaction between two small molecules not only with weak forces such as electrostatic, H bond, or pi-pi stacking... but also the possibility of forming covalent bonding. I have design the molecules that could interact via schiff base reaction. I have searched across the net, but I could not find a way to incorporate this covalent binding interaction into the simulation.
If possible, could you give me some hints for doing this? Maybe I should open up a new question for this later.
Thank you very much for your great help!
Hi,
is probably best to use CHARMM-GUI for obtaining CHARMM parameters. It should work fine.
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