I would like to dock a 15-residue peptide to a receptor, using the HADDOCK2.4 webserver. I have few questions:
Is the peptide allowed flexibility? If yes, are only the sidechains treated as flexible or also the backbone? We suspect that this peptide undergoes some order-to-disorder transition during binding.
Does the webserver submission form allow to tune the flexibility of the peptide. If so, could you suggest me which options should I consider?
The receptor has an acylated residue. This residue is part of the binding pocket and it might play a role. Will the acylated residue be simulated or just disregarded, being a non-standard amino acid?
Hi,
thanks for the links! I had a look at the non-standard amino acids and the one I am looking for is not there, unfortunately. What happens if I change to HETATM this non-standard amino acid? Will HADDOCK recognize it?
A more specific question on peptide docking. Is there any way to have HADDOCK explore the flexibility of the peptide backbone or this is only achievable by running separately MD on the peptide?
thanks for the links! I had a look at the non-standard amino acids and the one I am looking for is not there, unfortunately. What happens if I change to HETATM this non-standard amino acid? Will HADDOCK recognize it?
It would recognise it but the problem will be it will be disconnected from the other residues.
A more specific question on peptide docking. Is there any way to have HADDOCK explore the flexibility of the peptide backbone or this is only achievable by running separately MD on the peptide?
Probably time to read our papers on protein-peptide docking and check the tutorials - all linked from the best practice guide.
Short answer: Yes backbone flexibility is handled by defaults, but don’t expect folding events to take place. Check our docking strategy for peptide in our papers:
HADDOCKing of the p53 N-terminal peptide to MDM2: This tutorial introduces protein-peptide docking using the HADDOCK web server. It also introduces the CPORT web server for interface prediction, based on evolutionary conservation and other biophysical properties.
It would recognise it but the problem will be it will be disconnected from the other residues.
Sure that is not a problem in this exploratory phase (it will become a problem later), as long as the non-standard amino acid stays in place.
Thanks for the clarifications and especially for the reference to your 2015 paper. The strategy presented there is rather interesting and I would like to ask a couple of questions regarding it.
Having three peptide conformations to explore the “main” docking scenarios is an interesting idea. However, this might be a limited number of states. If I want to probe in-between scenarios (e.g. a partially unfolded helical peptide), shall I add another model structure to the input peptide file?
Once the run is over, I imagine that the different clusters will represent different poses + different peptide conformations. Is it correct to say that if I take the “best cluster” I will have the combination of most probable pose + peptide conformation both of which represent a minimum of the energy?
Sure that is not a problem in this exploratory phase (it will become a problem later), as long as the non-standard amino acid stays in place.
It will not most likely, unless you define some additional distance restraints to keep it connected.
Having three peptide conformations to explore the “main” docking scenarios is an interesting idea. However, this might be a limited number of states. If I want to probe in-between scenarios (e.g. a partially unfolded helical peptide), shall I add another model structure to the input peptide file?
You can of course provide more conformations, but not too many is my advise, otherwise you get I would like to call a “dilution” problem.
Once the run is over, I imagine that the different clusters will represent different poses + different peptide conformations. Is it correct to say that if I take the “best cluster” I will have the combination of most probable pose + peptide conformation both of which represent a minimum of the energy?
Always look at more than one solution. Difficult to predict a-priori how the results of your run will look like.