So...I'm investigating two proteins.
1 - Let's call it receptor protein, It's a transmembrane protein, located in the nuclear envelope
2 - It's the 'ligand protein', which resides in cyto- and nucleoplasm
I found that inhibition of a kinase prevents 1 and 2 from interacting. It's described in literature, that 2 is phosphorylated downstream of this kinase.
Is there any chance to get some hints from computational biology, whether the interaction is influenced by this phosphorylation?
Thank you in advance for your help
Yes it is possible to see the effect of phosphorylation on the interaction of two proteins. First you should have structure of two proteins. You can predict the physical interaction using protein-protein docking software such as Cluspro, Hex . Once you get the complex which support ur hypothesis, then u can setup MD simulation.
Thank you Vikash for your answer!
The structures are in PDB, so they are available. So I modifiy the structure of 2 by adding a phosphate at the Serine residue. And what should be done next? (Sorry I am totally new to this,,,)
I guess, there has to be some structure refinement, as the phosphorylation affects the structure of the protein. Is that something you would do with NAMD/GROMACS etc.?
Then docking, and then MD...?
It would be great, if you could recommend some basic literature.....
Once you have phosphorylated the residues, you try minimizing complex before docking to remove any steric clashes. Alternatively I will suggest you to use Vienna PTM webserver as there you select minimization along with the automated phosphorylation. It is optimized for Gromacs and you can use the rtp entry as well.
Is there a structure of the protein-protein complex available? If not, than the problem becomes quite difficult. The available protein-protein docking programs/servers are likely to give you false answers and if you don't have any experimental data concerning the complex (not necessarily xray, but some other data which at least point which residues are close to eachother) you won't be able to validate it. This is the crucial step to get things right so do a literature search on this.
If you have a good protein-protein structure: MD of the phosphorylated and native structure using any available software and their comparison may give you some hints on the changes on molecular level.
Thank you Bartosz for your answer!
Unfortunately there is no structure of the complex available. Furthermore, there is little known on the actual interaction mode of these two proteins.
The 'receptor'-protein is a transmembrane protein in the nuclear membrane, so it's likely that the 'ligand'-protein binds to residues exposed to the cyto-/ or nucleosol.
For the ligand-protein I found that inhibiton of a kinase (which subsequently should inhibit phosphorylation) prevents interaction. So a straightforward hypothesis is, that the phosphorylated serine is involved in the protein-protein-interaction.
Would you think this is sufficient data to go on with docking/MD?
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