Multidomain flexible docking

Hi,

I would like to set up a multidomain flexible docking simulation as desrcibed in Karaca, E. & Bonvin, A. M. J. J. A multidomain flexible docking approach to deal with large conformational changes in the modeling of biomolecular complexes. Structure, 19, 555–565 (2011). I can follow the set up protocol described in the paper on the webserver (i.e., keeping the proper termini neutral, making the bridging residues flexible, using center of mass restraint) with the exception of the connectivity restraints between two domains for it0/it1 versus final refinement (Fig. 2 in the paper). My question is how do I add the second 1.3 A distance restraint during the final refinement?

Thanks is advance your your help!

Cheers,
Mike

Hi Mike

Upload the restraints under the hydrogen bond category.

→ Docking parameter tab of the 2.4 portal → Dihedral and hydrogen bond restraints

And to tell HADDOCK to only use it at the final stage on the same page:

→ Restraint energy constants → Energy constants for hydrogen bond restraints → set the 1st iteration to itw

Note that this does require guru access.

Also do realize that the distance will never reach 1.3A because of van der Waals repulsions.
You will have to refine the complex after that to restore property the covalent bond.

This can be done by defining again your various domains as one molecule (same chainID) and using for example our refinement interface.

Cheers
Alexandre

Alexandre,

Thank you very much for your help. Very clear and makes perfect sense!! (I have guru access)

Let’s see how it goes.

Thanks,
Mike