binder-designlisted

# Binder Design Tool Selection ## Decision tree ``` De novo binder design? │ ├─ Standard target → BoltzGen (recommended) │ All-atom output (no separate ProteinMPNN step needed) │ Better for ligand/small molecule binding │ Single-step design (backbone + sequence + side chains) │ ├─ Need diversity/exploration → RFdiffusion + ProteinMPNN │ Maximum backbone diversity │ Two-step: backbone then sequence │ ├─ Integrated validation → BindCraft │ Built-in AF2 validation │ End-to-end pipeline │ ├─ Ligand binding → BoltzGen ✓ │ All-atom diffusion handles ligand context │ ├─ Peptide/nanobody → Germinal │ VHH/nanobody design │ Germline-aware optimization │ └─ Antibody/Nanobody +-- VHH design --> germinal skill ``` ## Tool comparison | Tool | Strengths | Weaknesses | Best For | |------|-----------|------------|----------| | BoltzGen | All-atom, single-step, ligand-aware | Higher GPU requirement | Standard (recommended) | | BindCraft | End-to-end, built-in AF2 validation | Less diverse | Production campaigns | | RFdiffusion | High diversity, fast | Requires ProteinMPNN | Exploration, diversity | | Germinal | Nanobody/VHH design | Specialized | Antibody optimization | ## Recommended Pipeline: BoltzGen → Chai → QC BoltzGen provides all-atom design with built-in side-chain packing: ``` Target → BoltzGen → Validate → Filter (pdb) (all-atom) (chai) (qc) ``` ### 1. Target preparation ```bash # Fetch structure from PDB # Use pdb skill for guidance ``` - Trim