Dealing with unstructured part and membrane composition in LightDock+HADDOCK membrane proteins tutorial

HADDOCK
1

Hi everyone!
I am trying to dock a protein, a chemokine, to the surface of a chemokine receptor(GPCR) inserted in membrane following LightDock + Haddock membrane proteins tutorial. (LightDock+HADDOCK membrane proteins tutorial – Bonvin Lab)

I have two questions for you.

  1. N terminal domain: Some experimental studies suggest that these regions are involved in the protein-ligand binding, for this reason I want to maintain the unstructured N terminals domain for both the receptor and the ligand in my final model. I was wondering if there is a way to take into account the flexibility of both partners in the LightDock + Haddock membrane proteins tutorial.

  2. Membrane: The GPCR of interest has not been crystallized yet, so I used an AlphaFold model. I started the protocol using a membrane mimicking a physiological membrane in term of lipids composition (in addiction to DPPC, contain also POPC,DOPC,POPE,DOPE,DPP1,POPS,DAPA,BNSM,CHOL ). I removed all lipids beads except those representing the phosphate groups, as indicated by the protocol.
    The problem is that the unstructured part of the ligand has been docked inside the holes of the membrane created by the missing beads relative to non phosphate-containing lipids (e.g. cholesterol).
    I would like to know:
    Can I somehow model a composition of the membrane different from the one reported in the tutorial?
    Or is it better to use the standard membrane reported in the tutorial?

2

The short answer is: trim the unstructured part - it will clearly not fold during docking, but only give problems.