drug-binding-site-definition

drug-binding-site-definition

Goal

To produce a standardized docking / simulation box definition (center coordinates + box dimensions in Angstroms) that downstream skills such as drug-docking-vina and drug-complex-system-builder can consume directly.

Choosing the Right Mode

Use this decision tree to pick the appropriate approach:

Do you have a reference ligand positioned in the binding site?
  |-- YES --> Mode A (co-crystal ligand)
  |-- NO
       Do you know the key binding-site residues (from literature, mutagenesis, etc.)?
         |-- YES --> Mode B (residue list)
         |-- NO
              Do you have a closely related protein with a known binding site?
                |-- YES --> Superimpose structures, transfer the ligand,
                |           then use Mode A on the transferred ligand.
                |           (See "When You Have No Binding-Site Information" below.)
                |-- NO  --> Run computational pocket prediction first
                            (see "When You Have No Binding-Site Information" below),
                            then feed results into Mode A or B.

If you already have a saved box JSON from a prior run, use Mode C to reload it.

Instructions

1. Mode A: Box from a co-crystal ligand (most common)

If you have a reference ligand already positioned in the binding site (PDB, SDF, MOL2, or PDBQT), compute the box automatically:

# Env: drugdisc-agent
python .agents/skills/drug-binding-site-definition/scripts/define_binding_site.py \
  --mode ligand \
  --ligand_file docking/inputs/reference_ligand.sdf \
  --padding 6.0 \
  --min_size 20.0 \
  --output_json docking/inputs/binding_site.json

Key parameters:

• --padding: buffer added to the ligand bounding box on each side (default 6.0 A). Use 4-5 A for tight/buried pockets, 8-10 A for shallow or allosteric sites.
• --min_size: minimum box edge length per axis (default 20.0 A).