It’s my first time trying to do docking and using Haddock, so I would like to ask any of you for some tips and pointers. I’m trying to simulate the covalent binding of a peptide with a modified side chain to a protein.
The modified side chain doesn’t exist in the PDB library, so I defined the whole residue with HETATM command, and used an CNS file to connect the N ter and Cter of the residue to the next and previous residue.
After docking I’ve noticed though that my modified residue had drifted away. How can I prevent that?
Also, I’m using Haddock, but without any experimental infos on the protein-peptide interaction apart from the bound lenght I want to create. So I was wondering if I want to perform ab initio calculations, which parameters should I choose?
Since it is defined as HETATM it will be disconnected from the remaining of your peptide.
You could define a few distance restraints to keep it in place.
Did you check if your modified residue is not supported by HADDOCK?
Also, I’m using Haddock, but without any experimental infos on the protein-peptide interaction apart from the bound lenght I want to create. So I was wondering if I want to perform ab initio calculations, which parameters should I choose?
You mention covalent binding. Do you know the chemistry, i.e. to which groups on the protein could your modified residue bind?
You could use this info to define an ambiguous restraint.
Thanks so much for your help!
Yes I’ve create a file to define distance between my residue and other amino acid, and upload it as unambigous restraint files:
assign (segid B and name C03 and resi 105) (segid A and name NZ and resi 131) 1.47 0.1 0.1
assign (segid B and name C and resi 105) (segid B and name N and resi 106) 1.32 0.01 0.01
assign (segid B and name N and resi 105) (segid B and name C and resi 104) 1.32 0.01 0.01
And I also used LINK command in the pdb file to specify the link between my residue (MAT) with the other amino acid.
LINK N MAT 105 C ASP 104 1555 1555 1.31
LINK C MAT 105 N GLY 106 1555 1555 1.31
Also yes, I’ve checked but my modified amino acid isn’t supported by Haddock, I’m attaching a warhead, so I will need to modify either pdb file or upload a tbl file to specify interactions. Also I do know how and where the residue is supposed to bind, but even so, when I specify the bound lenght as unambigous restraint, the residue still drifts away. I have Guru access by the way.
Yes I’ve create a file to define distance between my residue and other amino acid, and upload it as unambigous restraint files:
assign (segid B and name C03 and resi 105) (segid A and name NZ and resi 131) 1.47 0.1 0.1
This one is an intermolecular distance restraint… but you were saying you don’t know where you peptide gets covalently attached…
assign (segid B and name C and resi 105) (segid B and name N and resi 106) 1.32 0.01 0.01
assign (segid B and name N and resi 105) (segid B and name C and resi 104) 1.32 0.01 0.01
And I also used LINK command in the pdb file to specify the link between my residue (MAT) with the other amino acid
LINK is irrelevant - does not get used.
Can you share your peptide/protein (via direct email)?
And/or a link to your docking results?