Controlling orientation of dimers

HADDOCK
1

I have been trying to dock a symmetrical GPCR homodimer, based around an interface using residues predicted by the PISA server (PDBe < PISA < EMBL-EBI).

I have tried enabling both C2 symmetry restraints and also NCS restraints, but always seem to end up with dimer structures that are anti parallel. Is there something I am missing that can reduce the chance of generating an anti parallel dimer?

I did also wonder if anyone had experience with listing lots of residues vs one or two resulting in particularly different outcomes?

2

That’s a tricky one. The simplest way to try to enforce // orientation would be to define e.g. two distance restraints between two atoms picked at the center of the GPCR at the top and at the bottom.
You should estimate what the upper limit for that distance should be based on the diameter of your GPRCs.

This might prevent anti// orientations.

3

Wonderful, I will give this a go. I take it that the best way to this is through a HADDOCK restraints TBL file with restraints that will always be enforced (unambiguous restraints)?

4

That’s the idea, yes