As we know that there is acid expansion of protein when we change the native ph of the protein. I want to prepare a protein at ph 4.7 (protonation state, as assay system was set to 4.7 ph) which is crystallized at ph 7.5. So for this protein, i want to consider the acid expansion effect in the docking study. So can anyone suggest me how to check the effect of variable ph range (acid expansion) on the protein structure by Gromacs MD simulation?
you could get product of those ph ranges, run invivo or invitro analysisi on protein comc.
Dear Mahender Singh,
1)Try to use the PDB2PQR server:
http://nbcr-222.ucsd.edu/pdb2pqr_1.9.0/
At the "Available options:" change the pH to 4.7
2) Run the pdb2gmx program, using the flags -lys, -arg, -asp, -glu, -gln and -his to create gro and top files at the pH 4.7 protonation state.
Kind regards,
Arlan.
You can do constant pH simulations in Gromacs. Just go through links provided which gives you basic idea about setting up a constant pH simulation in Gromacs.
Attachment is a tutorial prepared by some one, I found useful.
https://www.mpibpc.mpg.de/247796/usage
https://www.mpibpc.mpg.de/grubmueller/constpH
thank you all
@Kartheek Joshua
I want to simulate the acid expansion effect of protein with change in the ph of solavent i.e say for a 100 ns simulation ph will varies from 2 to 10 ?
I have not come across these kind of simulations so far, but writing to gromacs mailing list may help.
In theory this is doable.
If I understand your point -
prepare your system at ph 7.5
Simulate it for a while and after the system has equilibrated - get the final frame from it. Its up to you really - you can either take the ensemble average of your frames in simulation once they had equilibrated and consider the average as the representative conformation of the protein at that ph or just work with the final frame.
Using the final/ensemble average frame which is basically just a coordinate file (PDB) prepare a new system where you have the ph at 8, if you want to go up to 10 or at ph 7 if you want to go down to two. At each change over of ph you need to let the system equilibrate capturing the entire behaviour of your protein at that ph and repeat the process. You need to perform very subtle transitions depending on the sensitivity of your protein, even 0.5 like i mentioned might be too much. So you will need to work on how much is the right amount.
You will now have trajectories in each ph and using simple trajectory operations you can connect all of them together in order and observe your system as it transitions from ph 2 to ph 10.
Note:
Combining the trajectory is only for visualization purposes. You should perform the analysis on the frames you collected once the system has equilibrated.
Hope this helps.
Best,
/A
@Ashar J Malik
thank you for your suggestion.
I think this is the only way, at present to do this task
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