How to introduce the cryo-EM restraint in protein-small-molecule docking

HADDOCK
1

Hello, I am a rookie in protein-small-molecule docking, I would appreciate it if you could give some suggestions.

I have read two publications about HADDOCK: (1) Integrative Modeling of Biomolecular Complexes: HADDOCKing with Cryo-Electron Microscopy Data (Structure, 2015); (2) Shape-Restrained Modeling of Protein-Small-Molecule Complexes with High Ambiguity Driven DOCKing (J. Chem. Inf. Model, 2021).

And I was wondering if I could introduce the cryo-EM restraint of the small molecule when using HADDOCK to perform protein-small-molecule docking?

Similar work has been reported (GemSpot: A Pipeline for Robust Modeling of Ligands into Cryo-EM Maps, Structure, 2020), and it was integrated into the Glide pipeline of Schrodinger software.

Thank you in advance!

2

Seems to me an overkill to put EM restraints for docking… For sure it would not make much sense in HADDOCK. The shape protocol should work much better. There are ways of transforming the EM density of the ligand into shapes (i.e. collection of beads) (e.g. in the ATSAS suite).