Active residues in docking


#1

In protein-ligand docking, for active residues do I consider the residues that make H bonds between the protein and the ligand or do I consider all the residues that interact (for example via van der waals). Ty!


#2

Hello,

This will sightly depend on how confident you are about the binding mode of your complex. It seems that you already know for sure what residues will interact and how, right?
If this is the case, and you do not want to sample much your solutions, then you might want to go for unambiguous restraints between the residues atoms and the ligand ones.

If you have some uncertainty, then any residue interacting with the ligand could be added to the list of active residues (and then generate ambiguous restraints this time.) HADDOCK will model, hopefully correctly, the potential H-bonds.

Anyway, several runs with different setups can be done. Then your understanding of the system will certainly make you decide which ones are the most relevant.

Hope this will help,

Mikael


#3

Are you talking about the field that says “You can supply a HADDOCK restraints TBL file with restraints that will always be enforced (unambiguous restraints)” ? This file contains the residues that interact with each other, having into account that I want to do a protein-peptide docking?

Thank you


#4

Ah ok, you stated protein-ligand so I was assuming your were doing a docking between a small molecule (ligand) and a protein receptor, sorry for the misunderstanding.

If you do protein-peptide docking I will first advise you, if you didn’t yet, to read our article/protocol for protein-peptide docking: https://link.springer.com/protocol/10.1007%2F978-1-4939-2285-7_10

The default protocol is defining all peptide residues as passive. If you have some good ideas about which residues of the peptide must interact, I would advise you to put them as active. Let the rest of the peptide as passive. The potential binding interface of the protein is defined as active in our protocol, I would not change that.

Good luck,

Mikael


#5

And to add to that - have a look at our online tutorial for peptide-ligand docking:

This one uses MD clusters as input for the peptide, but I would recommend to start simple with the three conformations described in our article.

(it is actually part of a larger tutorial in the context of a master course):


#6

My bad… I know each residues interact with each other, isn’t there any field or level that I can put that information?


#7

I mean, I only want that the last part of my peptide to interact with the protein, the first part I don’t want it to interact at all…


#8

You can define specific restraints between residues if you wish, and upload those as ambig or rather unambiguous restraints in the expert interface (or simply as active residues in the easy interface).

But if you don’t want the remaining of your peptide to interact, simplest would be not to include most of that region during the modelling - you can then draw/create spaghettis as you wish :slight_smile: