Protein-peptide docking starting from crystal structure

Dear Users,

Hello, I want to model a protein-peptide complex. We have solved a crystal structure of the complex however several residues of the peptide were missing in this crystal structure. On the other hand, we have proved by mutagenesis/ITC experiments that one of the missing residues could be involved in interacting with the protein.
So, my question is, can haddock deal with this situation? Should I extract distance restraints from the crystal structure for docking and dock with the expert interface? Or can I define active residues in the refinement interface?

Any suggestions would be appreciated, thanks!

Dear jhpanda,

You can indeed use the expert interface to provide both unambiguous (extracted from the crystal structure) and ambiguous (derived from mutagenesis/ITC experiments) distance restraints. The refinement interface will not allow you to add active residues but only to optimize an existing interface.

Depending how many residues of the peptide are missing in your crystal structure, you may want to start from an ensemble of models to account for some flexibility. The sampling should obviously be limited to the missing residues of the peptide (you do not want to modify the structure of the residues that are present in the crystal).

You can also use the dihedral distance restraints ( to keep the structure “rigid” upon it0/it1 and maybe release the dihedral restraints in the water stage.

Good luck