RF Diffusion

Runs RFdiffusion to generate or redesign protein structures. Supports unconditional generation (by length), conditional generation using an input PDB and contigs, and scaffold-guided/fold-conditioned design via optional configuration nodes. Can optionally output trajectory PDBs from the diffusion process and supports deterministic runs via a base seed.

Usage

Use this node to create new protein backbones or redesign regions around fixed motifs. Typical workflows: (1) Unconditional generation by providing only a length range in contigs; (2) Conditional generation by providing an input PDB and contigs describing fixed and flexible regions; (3) Scaffold-guided or fold-conditioned design by connecting a Scaffold Guided Config. Optionally plug in Symmetry, Contigmap, Denoiser, and Potentials configs to control sampling behavior. Choose PROD for normal execution, TEST for fast dry-runs, or MOCK to return predefined results.

Inputs

Field	Required	Type	Description	Example
checkpoint	True	CHOICE	Which pretrained checkpoint to use. Auto automatically selects a compatible checkpoint based on inputs; others force a specific checkpoint.	Auto
write_trajectory	True	BOOLEAN	Whether to include diffusion trajectory PDBs (Xt-1 and pX0) in the outputs.	True
model_runner	True	CHOICE	Sampler to use during generation.	SelfConditioning
align_motif	True	BOOLEAN	If true, aligns the model's predicted motif to the provided motif in conditional modes.	True
final_step	True	INT	Reverse diffusion step to stop at (1-50). Larger values reduce compute but may affect quality.	1
contigs	True	STRING	Sequence layout specification. Unconditional: only length range (e.g., 100-100). Conditional: combine fixed regions (A10-25), flexible gaps (5-15), and chain breaks (/0). For partial diffusion (partial_T != 50), must match the exact residue order/count of input PDB.	5-15/A10-25/30-40/0 B1-100
hotspot_res	True	STRING	Residue positions on the TARGET protein to optimize interactions against (used in PPI/binder design). Leave empty unless a target is provided via Scaffold Guided Config.
partial_T	True	INT	Set to 50 to disable partial diffusion. Values 0-49 start denoising from a partially noised structure. Requires input_pdb when enabled.	50
seed	True	INT	Base seed for deterministic generation. Derived seeds are used for each design internally.	42
mode	True	CHOICE	MOCK returns predefined data, PROD executes the service, TEST runs a faster minimal-parameter version (disables trajectory and cautious mode, sets final_step to 49).	PROD
timeout	True	INT	Timeout in seconds for the run.	600
input_pdb	False	PDB	Optional initial PDB for conditional design or partial diffusion. Required for partial diffusion (partial_T != 50).	{'pdb_name': 'input_structure.pdb', 'pdb_content': ''}
symmetry_config	False	RFDIFFUSION_SYMMETRY_CONFIG	Additional symmetry settings. Connect from 'RF Diffusion Symmetry Config'.	{'symmetry': 'c2', 'recenter': True}
contigmap_config	False	RFDIFFUSION_CONTIGMAP_CONFIG	Sequence/structure masking and length settings. Connect from 'RF Diffusion Contigmap Config'.	{'inpaint_seq': 'A10-20', 'length': '100-150'}
denoiser_config	False	RFDIFFUSION_DENOISER_CONFIG	Noise schedule customization. Connect from 'RF Diffusion Denoiser Config'.	{'noise_scale_ca': 1.0, 'final_noise_scale_ca': 1.0}
potentials_config	False	RFDIFFUSION_POTENTIALS_CONFIG	Guiding potentials to steer generation. Connect from 'RF Diffusion Potentials Config'.	{'guiding_potentials': ['type:monomer_ROG,weight:1,min_dist:15'], 'guide_scale': 10}
scaffoldguided_config	False	RFDIFFUSION_SCAFFOLDGUIDED_CONFIG	Enable scaffold-guided/fold-conditioned design and optional target PPI context. Connect from 'RF Diffusion Scaffold Guided Config'.	{'scaffoldguided': True, 'target_pdb': True}

Outputs

Field	Type	Description	Example
generation.pdb	PDB	Final generated or redesigned protein structure.	{'pdb_name': 'generation_0.pdb', 'pdb_content': ''}
trajectory_Xt-1.pdb	PDB	Trajectory snapshot at Xt-1 (if write_trajectory is true; disabled in TEST mode).	{'pdb_name': 'trajectory_Xt-1_0.pdb', 'pdb_content': ''}
trajectory_pX0.pdb	PDB	Trajectory snapshot at pX0 (if write_trajectory is true; disabled in TEST mode).	{'pdb_name': 'trajectory_pX0_0.pdb', 'pdb_content': ''}

Important Notes

• Contigs format rules are strict. Unconditional generation must provide only a length range (e.g., 100-100). Conditional generation must include at least one fixed region with chain letters (e.g., A10-25), unless scaffold-guided design is enabled.
• Partial diffusion: set partial_T to 50 to disable. Any value 0-49 requires input_pdb and, for non-scaffold-guided runs, contigs must match the exact residue count/order of the input PDB.
• Unconditional generation forbids hotspot_res and any contigmap_config fields other than length.
• Hotspot residues require a target protein. If hotspot_res is provided, a target must be configured via Scaffold Guided Config (target_pdb).
• TEST mode automatically sets final_step to 49, disables trajectory outputs, and turns off cautious mode for speed.
• Seeds are used deterministically; per-output seeds are derived from the base seed.
• If write_trajectory is false (or in TEST mode), trajectory outputs may be empty or not populated.

Troubleshooting

• Error: 'Non empty contigs must be passed' or similar. Fix: For non-scaffold-guided runs, ensure contigs is provided and valid. In scaffold-guided mode, contigs may be omitted.
• Error: 'For partial diffusion sampling, expected input_pdb to be provided.' Fix: Supply input_pdb when partial_T is not 50, or set partial_T to 50 to disable partial diffusion.
• Error: 'For unconditional sampling, expected contigs to specify only length range' Fix: Use a format like 100-100 with no chain letters for unconditional mode.
• Error: 'For conditional sampling, expected contigs to specify least one fixed region' Fix: Include at least one region with a chain letter and residue range (e.g., A10-25) when not using scaffold-guided mode.
• Error: 'For unconditional sampling, expected hotspot_res to be empty' Fix: Clear hotspot_res when running unconditional generation.
• Error: 'Expected k to be empty' from contigmap settings. Fix: In unconditional mode, only length may be set in contigmap_config; clear other fields.
• Error about hotspot_res without target. Fix: Add a target protein via Scaffold Guided Config (target_pdb) or remove hotspot_res.
• No trajectory outputs returned. Fix: Ensure write_trajectory is true and not running in TEST mode; also confirm timeout is sufficient for full run.
• Timeouts. Fix: Increase timeout, reduce final_step, disable trajectory, or use TEST mode to validate configuration quickly.