RF Diffusion

Generates protein structures using RFdiffusion with optional conditional controls, symmetry, denoising schedules, guiding potentials, and scaffold-guided (fold-conditioned) settings. Supports both unconditional sequence-length based generation and conditional design from an input PDB, including partial diffusion and protein–protein interaction guidance. Deterministic by default using the provided seed, with optional trajectory outputs for analysis.

Usage

Use this node to design or sample protein backbones. For unconditional sampling, provide only a length range in contigs. For conditional design, supply an input PDB and specify contigs with fixed regions and flexible gaps; optionally enable scaffold-guided fold conditioning and PPI design via their respective config nodes. Connect optional configuration nodes to fine-tune symmetry, contig masking, denoising, and potentials. Choose PROD for real runs, TEST for quick checks, or MOCK to return precomputed demo results.

Inputs

Field	Required	Type	Description	Example
checkpoint	True	ENUM[Auto, Base, Complex_base, Complex_Fold_base, InpaintSeq, InpaintSeq_Fold, ActiveSite, Base_epoch8, Complex_beta]	Model checkpoint selection. Auto chooses the best checkpoint based on inputs; manual selection requires compatibility with your setup.	Auto
write_trajectory	True	BOOLEAN	If true, also outputs intermediate trajectory PDBs.	true
model_runner	True	ENUM[default, SelfConditioning, ScaffoldedSampler]	Sampler variant to run for the diffusion process.	SelfConditioning
align_motif	True	BOOLEAN	Aligns predicted motif to the input motif when applicable.	true
final_step	True	INT	Reverse diffusion stopping step (1–50). Larger values speed up inference by stopping earlier.	1
contigs	True	STRING	Defines sequence layout. Unconditional: length range only (e.g., 100-100). Conditional: combine fixed motifs (A10-25), flexible gaps (5-15), and chain breaks (/0). For partial diffusion (partial_T != 50), must fully match the input PDB’s residue count/order.	5-15/A10-25/30-40/0 B1-100
hotspot_res	True	STRING	Residues on the target protein to encourage interactions (PPI). Comma-separated chain+index (e.g., A30,A33). Leave empty unless a target protein is configured.	A30,A33,A34
partial_T	True	INT	Start timestep for denoising (0–50). Set 50 to disable (full diffusion). Values <50 enable partial diffusion and require an input PDB.	50
seed	True	INT	Base seed for deterministic generation.	42
mode	True	ENUM[MOCK, PROD, TEST]	Run mode. MOCK returns precomputed results, PROD runs the service, TEST uses minimal parameters for quick checks.	PROD
timeout	True	INT	Timeout in seconds for the service call (30–12000).	600
input_pdb	False	PDB	Input structure for conditional or partial diffusion. Required for partial_T < 50.	{'file_0.pdb': ''}
symmetry_config	False	RFDIFFUSION_SYMMETRY_CONFIG	Symmetry parameters. Connect from RF Diffusion Symmetry Config.	{'symmetry': 'c3', 'recenter': True, 'radius': 10}
contigmap_config	False	RFDIFFUSION_CONTIGMAP_CONFIG	Contig masking, inpainting, and length options. Connect from RF Diffusion Contigmap Config.	{'inpaint_seq': 'A10-20', 'length': '100-150'}
denoiser_config	False	RFDIFFUSION_DENOISER_CONFIG	Noise scaling and schedule settings. Connect from RF Diffusion Denoiser Config.	{'noise_scale_ca': 1.0, 'final_noise_scale_ca': 1.0, 'ca_noise_schedule_type': 'constant'}
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, 'guide_decay': 'constant'}
scaffoldguided_config	False	RFDIFFUSION_SCAFFOLDGUIDED_CONFIG	Fold-conditioning and scaffold-guided design parameters; supports PPI with target proteins. Connect from RF Diffusion Scaffold Guided Config.	{'scaffoldguided': True, 'scaffold_secstruc_adj': {'type': 'secstruc_adj_input', 'pdbs': {'file_0.pdb': ''}}}

Outputs

Field	Type	Description	Example
generation.pdb	PDB	Final generated protein structure(s).	{'design_0.pdb': ''}
trajectory_Xt-1.pdb	PDB	Intermediate trajectory at Xt-1, if write_trajectory is true.	{'design_0_Xt-1.pdb': ''}
trajectory_pX0.pdb	PDB	Predicted pX0 trajectory, if write_trajectory is true.	{'design_0_pX0.pdb': ''}

Important Notes

• Partial diffusion: Set partial_T to 50 to disable. Any value <50 requires an input PDB and a full contig layout matching the PDB’s residue order.
• Unconditional vs conditional: Unconditional requires contigs with length-only ranges (e.g., 100-100) and hotspot_res must be empty. Conditional requires at least one fixed region (e.g., A10-25) unless scaffold-guided mode is enabled.
• Scaffold-guided mode: contigs may be omitted because they are auto-generated from the scaffold. If specifying hotspot_res in scaffold-guided mode, you must also provide a target protein via Scaffold Guided Config.
• Determinism: The seed controls design numbering and enables deterministic outputs for the same configuration.
• Trajectory outputs: trajectory_Xt-1.pdb and trajectory_pX0.pdb are only returned when write_trajectory is true.
• Mode behavior: TEST mode reduces final_step and disables cautious mode and trajectories for speed; MOCK returns precomputed demo results; PROD performs real generation.
• Checkpoint Auto: Auto selects an appropriate checkpoint based on inputs; manual checkpoints may not support all configurations.
• Timeout: Ensure timeout is sufficient for complex runs; large systems or trajectories may require higher values.

Troubleshooting

• Error: Non empty contigs must be passed: Ensure contigs is provided unless using scaffold-guided mode, where contigs can be omitted.
• Error: For partial diffusion sampling, expected input_pdb to be provided: Supply an input PDB when partial_T < 50.
• Error: For unconditional sampling, expected contigs to specify only length range: Use formats like 100-100 and avoid chain letters in unconditional mode.
• Error: For unconditional sampling, expected hotspot_res to be empty: Remove hotspot_res for unconditional runs.
• Error: For unconditional sampling, expected <param> to be empty but got ...: In contigmap_config only length may be set; clear other contigmap fields in unconditional mode.
• Error: For conditional sampling, expected contigs to specify least one fixed region: Include at least one region with chain letters (e.g., A10-25) unless in scaffold-guided mode.
• Error: hotspot_res specified but no target protein configured: When using hotspot_res in scaffold-guided design, also provide target_pdb (and ideally target_pdbs) in the Scaffold Guided Config.
• Unexpected early stop or no trajectories in TEST: TEST mode forces final_step=49 and disables trajectory writing for speed; switch to PROD and enable write_trajectory.