Dear all,
I want to insert the drug at a certain distance from the membrane. The membrane is prepared in Charmm-GUI.
Do I have to remove water and ions from the membrane, add the drug molecule with the gmx insert_molecules command, and then add water and ions again?
Because I tried without removing water and ions and used the replace flag. In the minimization stage, the complex became Irregular.
Should I make a restraint position file for the drug?
And the last question, does anyone have experience using the Charmm-GUI to insert the drug? it means that instead of the peptide or protein file, import the PDB file of the drug and insert it in a certain distance.
I would be happy to know your opinions and get your advice.
I don’t understand what you mean with “the complex became irregular”. You should be able to use the -replace option of gmx insert-molecules. If water molecules get replaced I don’t think you need to do much. If ions get replace you can just run gmx genion again to make it net neutral.
If you want to restrain the drug, you will need to make a position restraints file for it. It might be good to have during equilibration.
I am thankful for your guidance.
Regarding the sentence you said is unclear, I will upload a file. I would be grateful if you could guide me to solve this problem.
Minimization: In this step, I have an error (Don’t Match atom in gro and forcefield.) To solve it, I changed the number of water molecules in the forcefield file.
Up to this step, the structure is normal.
when I do other steps, the structure looks strange.
How can I process the trajectory or coordinates afterward? Could this problem be related to the mdp file? I used the Tutorial 2: KALP15 files in DPPC to prepare the mdp file and made some changes.
I would avoid doing any trjconv steps before adding a box with editconf. Try just skipping those first three steps (do them when your simulations are finished, if if helps you visualising them).
Have you been able to resolve this now? I am currently trying same thing with different difficulties. Your response would be of great value to me. Thank you.
Hi,
I changed my method to do this work.
First, I remove water and ions from the membrane, then add the box to the membrane with this command:
gmx editconf -f membrane.gro -o membrane_box.gro -box x y z
x,y, and z are written in the final line of your membrane.gro file.
Second, add a box for the drug or ligand with this command:
gmx editconf -f drug.gro or drug.pdb -o drug_box.gro -box x y z – center a b c
x,y,z in command 2 is same x,y,z in command 1.
When you run command 1, Gromacs shows a message that includes the center of the box. a and b are in the same center of the membrane, and c is the distance that you want the drug insert there. c is the distance in the z coordinate.
Then run this command:
cat membrane_box.gro drug_box.gro > complex.gro
Now edit the complex.gro (line 2 and another extra line)
Add water, ions and other steps.
I actually started up with this approach of removing the water and ions from the membrane.
My challenge has been how to precisely position the protein/drug at a specified distance (0.5nm) from the topmost atom of the membrane (along the z-axis). The choice of the c is the problem as gromacs uses COM and not COG, so the COM may not necessarily be symmetrical and distance from COM to the lowest atom of the drug/protein may not necessarily be the z of the drug/protein divided by 2.
So, it becomes difficult to accurately insert it knowing if too close, it could introduce errors to the simulation or if too far from the membrane, it will require longer simulation time with lots of resource utilization.
in addition, the number of the output file was not continuous for large complex/systems formed (protein + membrane, over 200,000 atoms).
