Antibody design · Protein Design

RFantibody

(Work in Progress)

Design antibody or nanobody binders against a target structure.

Runs the whole RFantibody pipeline against a target and an HLT framework: antibody-finetuned RFdiffusion docks a backbone and rebuilds the chosen CDR loops, ProteinMPNN designs their sequences, and antibody-finetuned RF2 predicts the complex for filtering. The Antibody task designs a paired heavy/light framework; Nanobody designs a VHH.

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Framework The HLT-formatted scaffold whose CDR loops and dock are designed. The two bundled frameworks are the ones used in the RFantibody preprint; pick the one that matches the task. "Custom" converts the Chothia-numbered antibody PDB below into HLT format instead.

Target antigen PDB The antigen structure. Crop it to the region around the epitope: RFdiffusion and RF2 both scale as O(N^2) in residue count.

Antigen chains Comma-separated chain IDs to keep from the target PDB, for example A or A,B. Everything else in the file is dropped before the run.

Antibody PDB Read only when the framework is "Custom": a Chothia-numbered antibody structure, such as one downloaded from SAbDab. It is converted to HLT format using the chain IDs below.

Heavy chain Chain ID of the heavy chain in the antibody PDB.

Light chain Chain ID of the light chain in the antibody PDB.

Epitope hotspots Comma-separated target residues that define the epitope, written as a chain ID then a residue number: A305,A456. These use the target PDB's own chain IDs and numbering. RFantibody is sensitive to the choice; pilot a few designs first.

CDR loops to design Comma-separated loops: hcdr1, hcdr2, hcdr3, and in the Antibody task lcdr1, lcdr2, lcdr3. A loop left out keeps the framework's own sequence and structure through both the diffusion and the sequence-design stages.

HCDR1 length "auto" lets the model keep the framework loop's own length, or give a fixed length (7) or a range sampled per design (5-13).

HCDR2 length "auto" lets the model keep the framework loop's own length, or give a fixed length (7) or a range sampled per design (5-13).

HCDR3 length "auto" lets the model keep the framework loop's own length, or give a fixed length (7) or a range sampled per design (5-13).

LCDR1 length "auto" lets the model keep the framework loop's own length, or give a fixed length (7) or a range sampled per design (5-13).

LCDR2 length "auto" lets the model keep the framework loop's own length, or give a fixed length (7) or a range sampled per design (5-13).

LCDR3 length "auto" lets the model keep the framework loop's own length, or give a fixed length (7) or a range sampled per design (5-13).

Select CDR indices Replace the framework's own CDR annotations with the residue indices below, rather than trusting the Chothia ranges it was labelled with.

HCDR1 residues 1-indexed absolute residue numbers in the HLT framework (heavy chain first, then light), as 26-32 or 26,27,28. Used only when "Select CDR indices" is on; an empty box leaves that loop's existing annotation alone.

HCDR2 residues 1-indexed absolute residue numbers in the HLT framework (heavy chain first, then light), as 26-32 or 26,27,28. Used only when "Select CDR indices" is on; an empty box leaves that loop's existing annotation alone.

HCDR3 residues 1-indexed absolute residue numbers in the HLT framework (heavy chain first, then light), as 26-32 or 26,27,28. Used only when "Select CDR indices" is on; an empty box leaves that loop's existing annotation alone.

LCDR1 residues 1-indexed absolute residue numbers in the HLT framework (heavy chain first, then light), as 26-32 or 26,27,28. Used only when "Select CDR indices" is on; an empty box leaves that loop's existing annotation alone.

LCDR2 residues 1-indexed absolute residue numbers in the HLT framework (heavy chain first, then light), as 26-32 or 26,27,28. Used only when "Select CDR indices" is on; an empty box leaves that loop's existing annotation alone.

LCDR3 residues 1-indexed absolute residue numbers in the HLT framework (heavy chain first, then light), as 26-32 or 26,27,28. Used only when "Select CDR indices" is on; an empty box leaves that loop's existing annotation alone.

Use AbMPNN weights Run the sequence-design stage against antibody-specific AbMPNN weights instead of the ProteinMPNN checkpoint RFantibody ships. Requires ABMPNN_MODEL_PATH to be configured on the host.

Report epitope distance Include RFdiffusion's per-design C-beta distance from each hotspot to the nearest designed CDR residue, as the closest and the mean over hotspots. Needs hotspots to be set.

Backbone designs How many docked backbones the diffusion stage generates.

Sampling temperature ProteinMPNN sampling temperature; higher is more diverse and less confident.

Sequences per backbone How many CDR sequences ProteinMPNN designs onto each backbone.

Omitted amino acids One-letter codes ProteinMPNN may not place. X is always omitted; C is omitted by default to avoid unpaired cysteines.

Backbone noise Gaussian noise added to backbone coordinates before sequence design.

Neighbours per residue Size of ProteinMPNN's k-nearest-neighbour graph.

RF2 recycles Recycling iterations in the RF2 filtering stage. RFantibody's own examples use 10; fewer is faster and less confident.

Hotspots shown to RF2 Proportion of the hotspot residues revealed to RF2 when it predicts the designed complex. Showing all of them makes the prediction less independent of the design.

Keep diffusion trajectories Write RFdiffusion's per-step trajectory PDBs alongside the designs.

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