Docking a protein with a fatty acid side chain

Hello,
I have tried to do protein-protein docking where one of the proteins has a fatty acid chain. Even though the docking was successful, the fatty acid chain was removed and is not visible when I view the results in Pymol. The fatty acid chain is essential for my protein, so I really need this fatty acid chain to also be docked.

Is it possible to dock proteins with fatty acid chains using HADDOCK?

Thank you,
Pawel

Provided the fatty acid chain is defined as HETATM is will work.
And check the content of the HADDOCK PDB files. It’s not because you don’t see it in PyMol that it is not there…

Thanks for the reply.

However, I am completely new to all of this and I am unsure how I should proceed. Do I only have to change “ATOM” to “HETATM” for all the atoms of the fatty acid chain in the pdb file of the ligand? The fatty acid chain is attached to a Cys residue. Does the Cys residue also have to be in the HETATM format?

Once again, I am a complete beginner to all of this, so I would greatly appreciate your help.

Thanks,
Pawel

Yes you will have to change all "ATOM " to “HETATM” - don’t mess up the columns in doing that.

As for the covalent link to the CYS, I would define an ambiguous distance restraint between your fatty acid and the CYS sulfur atom to keep it in place since HADDOCK won’t generate the covalent bond

How exactly should I go about defining an ambiguous distance restraint? I have never done such a thing before.

I know that the file must be in the format:
assign (resid x and segid B) (residy and segid A) d0 d- d+

However, if you look at the image from my previous post, both the Cys residue and the fatty acid atoms are assigned as residue 20. So what would resid x and residy be?

What should d0 (target distance), d-, d+ (lower and upper distance margins) be? How do they exactly define the distance?

Thanks,
Pawel

Make the distance specific between two atoms, e.g.:

assign (resid x and name YYY and segid B) (resid y and name SG and segid A) d0 d- d+

And as distance simply measure the corresponding distance in your starting model and use that one, with e.g. values of 0.1 for d- and d+

Hello,

Thank you for the information. I am doing something very similar: I would like to dock an acylated holo protein ligand to a receptor. In particular, I would like to constrain the model such that the 9th carbon of the fatty acid chain is in a certain location in the binding pocket of the receptor, near the catalytic site. Do you recommend any settings to ensure that the acyl chain is situated in this fashion? I also saw some suggestions from Francesca Cantini’s post from 2016 which I will also try.

In a previous attempt using the easy interface, I docked an acyl-ACP to the receptor, however, the acyl chain retained its conformation from the input file and did not enter the binding pocket. I just received access for the expert interface so that I may incorporate distance restraints.

Thank you again for your time.

Define a specific distance restraint from your 9th carbon is at a specific distance range from the catalytic residues