I want to know if there is an online server for ligand-protein complex docking with another protein. The available renowned protein-protein docking servers like ClusPro, HADDOCK, PyDock etc. either remove or give an error when I try to upload the ligand-protein complex as the receptor pdb file. How can I verify that binding of a ligand to a receptor induces a conformational change or directly blocks the interacting surface in which the native proteins couldn’t bind effectively thereafter?
What kind of a ligand? I recommend CABS-dock for a protein in complex with a peptide ligand. It is very straightforward to use.
http://biocomp.chem.uw.edu.pl/CABSdock
Maksim Kouza Thank you Dr. Kouza for your answer, but I am dealing with a ligand with chemical structure (not peptide) and this server is incapable of doing that.
A workaround would be to dock the proteins first, e.g., using Rosetta. And then dock the compound to the complex (either manually or using a docking algorithm, such as Autodock).
My suggestion is Docking in Rosetta and checking the conformational changes of your protein measuring RMSD and other related values.Then use the complex in Autodock or any other suitable software as Prof. Kireev said. In some papers people use the naturally docked Crystal structures and use it as a reference. But to do this you should be lucky to find a Crystal structure bound(docked) with similar protein as yours. then you can change it with your target protein.
Farzane Jalalypour Dmitri Kireev Thank you very much for your suggestions. The docking of two proteins is not applicable to my system, because the ligand induces a conformational change in the first protein that the interaction between the two proteins does alter after this binding.
It is also possible to save an snapshot of your protein after docking with ligand. And use it to dock to other protein. ( without ligand but the induced conformation). Does it work for you?
Farzane Jalalypour The servers either result in an error or omit the ligand molecule when I provide a docked lig-pro structure.
My suggestion is First dock the protein (state 1) with ligand. ligand will induce conformational change and you can save the coordinates of protein(state 2) without ligand. then dock the state 2 of protein with the other protein in another server.
Farzane Jalalypour Consider that the ligand participates in chemical interactions with both proteins and it is sandwiched between these proteins. Then what should we do?
Please go through the link given below:
https://www.researchgate.net/post/Which_software_is_better_for_Protein-Protein_and_Ligand-protein_docking
Ardavan Abiri If i understand correctly, you have a protein-A with bound ligand and you wish to dock another protein-B to this ligand-protein complex.
Well its true that protein-protein docking softwares do not handle ligand well.
Now i am presuming you have two conformations of protein-A :- (1) its native state and (2) protein-A bound to the ligand which has undergone a conformational change upon binding.
In such cases you can first dock protein-A (native state) with protein-B and predict the interface. Then you can dock the alternative conformation of protein-A with protein-B.
You can then compare the top predicted interfaces between the two types of docking experiments. If the ligand disrupts the binding, then this comparison of docking experiments might provide an indicator.
hope this helps.
Thank you so much Dr. Mudgal. This method actually works fine when the ligand itself is not interacting with the two proteins but if the ligand is sandwiched between the two proteins or partially blocks the binding site of two proteins or entraps the binding residues of one protein without a conformational change (as the case of mine), this solution becomes inoperative.
- Badges
- Science topic
- Similar topics
- Bioinformatics
- Bioinformatics and Computational Biology