Cyclic peptide design combined with motif scaffolding

[aoberstein]

Dear Boltzgen Team,

I have a design case that I'm having trouble specifying in the "design_specification.yaml" file. I would like to design a cyclic-peptide binder to a target protein. The target protein comes from a pdb file (chain A), which was crystallized with a linear peptide substrate (chain B) bound to the active site. Chain A is an enzyme that modifies lysines in chain B. I'd like to redesign chain B as novel cyclic peptide binders to chain A with the lysine from the crystal structure 'motif scaffolded' in the active site of chain A. That is, I'd like to "extend" the lysine of chain B into a 12 - 18 AA macrocycle, but fix the 3D location of the lysine and extend the macrocycle around this amino acid.

I've tried a couple things in the .yaml file without much luck. My latest attempt was to add insertions around the lysine in chain B:

entities:
  - file:
      path: XXX.pdb
      include:
        - chain:
            id: A
        - chain:
            id: B

      design_insertions:
        - insertion:
            id: B
            res_index: 1
            num_residues: 5..17
            cyclic: True
        - insertion:
            id: B
            res_index: 2
            num_residues: 5..17
            cyclic: True
            
      binding_types:
        - chain:
            id: A
            binding: 185,188,209

Is this type of design possible? Can a more experienced user advise on how to get this to work?

Thanks, Adam