Simulation Breaks the system (separates both the chains of the Antibody)

User discussions
, , , ,
1

GROMACS version:
GROMACS modification: No

Hi @jalemkul
I have run the MD simulation (protein-lignad) by following your protocol (http://www.mdtutorials.com/gmx/complex/index.htm). Also at the end of simulation, I recentered and rewrapped the coordinates using gmx trjconv command. In MD simulation movie it gives weird outcome. I ran MD simulation for 200 ns.

Energy minimization graph is as follow.

image
image821×544 4.92 KB

since this portal doesn’t allow to upload video, please follow the link to see the video (protein_ligand_movie.mp4 - Google Drive). Also, I am attaching few frames of it.

At the begining:

image
image693×631 83.2 KB

after some time (around 50 ns):
image
image1502×727 115 KB

At near 100ns
image
image598×698 88.3 KB

at the end of simulation
image
image1681×703 107 KB

Throughout the simulation, both of the chains of Antibody keep joining and separating. Why is this happening?

Thanks

2

This is a simple PBC effect. Use gmx trjconv to center on one chain (not the default “Protein” group, you need to create an index group corresponding to one of the protein chains).

3

Thank you @jalemkul

First, Do I need to modify the index file by adding a group having atoms of Heavy or Light chain only. Then run the production MD commands.

gmx grompp -f md.mdp -c npt.gro -t npt.cpt -p topol.top -n index.ndx -o md_0_10.tpr

gmx mdrun -deffnm md_0_10

after MD production, gmx trjconv and then select one chain to be centered.

If not so could you please help me how to do that?

Thanks

4

After MD simulation, I created a group (light_chain) in index.ndx file and run the following command.
gmx trjconv -s MD.tpr -f MD.xtc -n index.ndx -o MD_center.xtc -center -pbc mol -ur compact

I selected the following options

select a group for centering-> light_chain
select a group for output-> system

Upon visualization same result. it separates both the chains apart.

image
image1192×540 127 KB

5

Hi Users, @jalemkul
Still struggling with this problem. Any help will be appreciated.

Thanks

6

Please render the box itself in your image.

7

Did you mean MD movie having solvent, ion and box?
In Chimera, I could’t find a way to get box boundaries. So, I tried it by uploading MD.gro and MD_recenter.xtc without deleting water/SOL molecules. Please find the url.

8

Your simulation box is too small to properly accommodate your protein complex, so one chain hits a periodic boundary and jumps. This is not resolvable via trjconv and you need to check your simulation carefully for minimum image violations.

9

Thanks for the suggestion.

How to determine the appropriate size/dimension of the box? I have used the box of same dimensions/size for a protein-protein (macromolecule) MD simulation and that worked perfectly. However, in Protein-Ligand MD simulation I’m facing this issue.

I am worried if I choose bigger box than required, lots of water molecule and ions might make simulation unnecessary heavy and this might impact the results.

10

You need a suitable spatial buffer around the solutes to avoid minimum image violations anyway, so if the solute is large, so too will your system. You can use something more efficient than a cubic box, like a rhombic dodecahedron, but editconf -d 1.0 is typical to get an appropriate box size.

11

I also have a similar problem. My system consist of two protein chains (protein-protein complex). After doing the md I see on trajectory that chains are divided and move out of box. I used procedure as for „protein in water”. I ask for help: on which stages and what changes I should make in order to exclude such situation: during protein-protein complex preparation, just before md or after md?