For the past month, I have been trying to model a tetrameric protein-ligand with a charmm forcefield. Noteworthy is that this protein is held together by disulfide bridges (ssbond). the dynamics of this protein however are very erratic(see rg below).
As I verify the trajectories, I have noticed that the disulfide bond is broken for all simulation cases.
Is there any way that one can set this s---s bond for my topology?
Do I have to modify my pdb file for charmm to understand it?
I would like to refer this question to you Dr. Justin Lemkul as you are great expert on the field
Best regards
Rg is a poor criterion for assessing the stability of folded proteins. A few disordered termini (common) and your analysis loses meaning.
The disulfide is either formed or it is not. It cannot, by definition, break during the simulation. Either it is there in the topology or it isn't. If visualizing the trajectory leads you to believe the bond "breaks" this is just a visualization artifact due to poor guessing of bonds by the software.
pdb2mgx tells you which disulfides it is linking. If it is incorrect at this stage you need to stop and obtain the proper state before doing a simulation.
You may refer to our recently published paper where we have introduced disulfide bond following the required criterion. Please follow the link: https://www.researchgate.net/publication/285894972_A_multi-subunit_based_thermodynamically_stable_model_vaccine_using_combined_immunoinformatics_and_protein_structure_based_approach?ev=prf_pub
Article A multi-subunit based, thermodynamically stable model vaccin...
Rg is a poor criterion for assessing the stability of folded proteins. A few disordered termini (common) and your analysis loses meaning.
The disulfide is either formed or it is not. It cannot, by definition, break during the simulation. Either it is there in the topology or it isn't. If visualizing the trajectory leads you to believe the bond "breaks" this is just a visualization artifact due to poor guessing of bonds by the software.
pdb2mgx tells you which disulfides it is linking. If it is incorrect at this stage you need to stop and obtain the proper state before doing a simulation.
If you can, please post the pdb file along with the topology (.top and .itp). I think you topology is not defined properly. Is it available in the PDB website or you have made it manually? If the later is true, where did you get the topology from?
One more thing, does only the S-S break? or some other bonds too?
This may happen due to wrong charges on the atoms which is not meant for charmm.
As Justin mentioned, if a bond is there (defined properly) in the initial structure, it can not break during the simulation.
So if possible please show those files.
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