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name: rfd3-reference description: RFdiffusion3 protein design reference. Use when working with RFD3, contigs, symmetry, hotspots, fixed atoms, RASA conditioning, H-bond conditioning, or Foundry API. Covers all input parameters, design types, and best practices.

RFdiffusion3 Reference Skill

Full documentation: docs/plans/2026-01-15-rfd3-comprehensive-skill.md

Quick Reference

Contig Syntax

Copy"60-80"              → Single chain, 60-80 residues
"60-80,/0,60-80"     → Two chains
"A10-50,/0,40-60"    → Keep A10-50, add new chain
"5-12,A10,3-8,A15"   → Scaffold around fixed residues

Key Parameters

Symmetry Types

• Cyclic: c2, c3, c4, ... (n copies around axis)
• Dihedral: d2, d3, d4, ... (2n copies)
• Platonic: t, o, i (use low_memory_mode=True)

CRITICAL: Guiding Potentials NOT SUPPORTED

substrate_contacts, olig_contacts, monomer_ROG are RFdiffusion v1/v2 CLI features - NOT available in Foundry API.

Design Types

1. Small molecule binder: Fix ligand atoms + hotspots
2. Protein binder: Target chain + hotspot residues
3. Enzyme design: Scaffold around fixed catalytic residues
4. Symmetric oligomer: Single monomer + symmetry flag
5. Metal binding: Fix coordinating atoms + metal

Example: Protein Binder

Copy{
    "contig": "B1-200,/0,60-100",
    "select_hotspots": {"B": "45,48,52,89,93"},
    "num_designs": 100
}

Best Practices

• Always diffusion_batch_size=1 for symmetry
• Pre-symmetrize motifs to canonical axes
• H-bond success rate ~37% (expected)
• Generate many designs for diversity