ProtenixScore

This repo was inspired by AF3Score (https://github.com/Mingchenchen/AF3Score).

Score existing protein structures (PDB or CIF) with the Protenix confidence head, without running diffusion. ProtenixScore is designed for fast, reproducible "score-only" evaluation of fixed coordinates and is suitable for batch pipelines. In practice it is typically ~2.5-3x faster than running the full Protenix inference pipeline when you only need confidence scoring.

Key features

• Score-only mode: uses provided coordinates, no diffusion sampling.
• PDB or CIF input, with automatic PDB -> CIF conversion.
• Per-structure outputs plus an aggregate CSV summary.
• Structural-template scoring support for the cytokineking Protenix fork.
• Optional deterministic MSA resolution with map/shared/cache/fetch fallback.
• ipSAE metrics (AF3Score-style) computed from Protenix token-pair PAE.

Requirements

• This repo checked out locally.
• Protenix fork installed (use install_protenixscore.sh).
• Python 3.11 environment with Protenix dependencies installed (conda or existing).
• Protenix checkpoint + CCD/data cache (downloaded by the install script unless skipped).

Install (recommended)

Clone this repo, then run the install script from the repo root:

git clone https://github.com/cytokineking/ProtenixScore
cd protenixscore
./install_protenixscore.sh

This clones the Protenix fork (with the Protenix v2 merge and score-only support), installs dependencies, and downloads weights/CCD data unless skipped. By default it installs the protenix-v2 checkpoint. It also wires up PROTENIX_CHECKPOINT_DIR and PROTENIX_DATA_ROOT_DIR (conda activation or printed for manual export). See ./install_protenixscore.sh --help for options.

By default, install_protenixscore.sh follows the configured Protenix fork branch. Pass --commit <sha> only when you want to pin a specific Protenix revision. The installer downloads the protenix-v2 checkpoint by default, and the CLI also defaults to --model_name protenix-v2. If you want to score with the older v1 base model, install that checkpoint with --model-name protenix_base_default_v1.0.0 and then pass --model_name protenix_base_default_v1.0.0 when scoring. The installer downloads only the selected checkpoint, so if you later want to score with another model you will need to rerun the installer with --model-name or place that model's .pt file into PROTENIX_CHECKPOINT_DIR.

If you keep multiple Protenix checkouts around, set PROTENIX_REPO_DIR=/path/to/Protenix_fork before running python -m protenixscore ... or python benchmark.py ... to force discovery to use that exact checkout.

Protenix original repository: https://github.com/bytedance/Protenix

Fork used by the install script: https://github.com/cytokineking/Protenix

Quickstart

After installing (and activating the environment if you used conda), validate the installation using the included test PDBs (single file):

python -m protenixscore score \
  --input ./test_pdbs/1_PDL1-freebindcraft-2_l141_s788784_mpnn6_model1.pdb \
  --output ./score_out

Validate the installation using the included test PDBs (entire folder):

python -m protenixscore score \
  --input ./test_pdbs \
  --output ./score_out \
  --recursive

Interactive guided mode:

python -m protenixscore interactive

Outputs

For each input structure sample, outputs are written to:

<output>/
  summary.csv
  failed_records.txt
  msa_resolution_summary.json
  template_resolution_summary.json
  <sample>/
    summary_confidence.json
    full_confidence.json
    chain_id_map.json
    msa_resolution.json
    template_resolution.json
    missing_atoms.json   (only if missing atoms were detected)

Notes:

• summary.csv is written when at least one structure is successfully scored.
• failed_records.txt is written only if one or more inputs fail.
• chain_id_map.json records the mapping between Protenix internal chain IDs and source chain IDs.
• msa_resolution.json records where each chain's MSA came from (single|map|shared|cache|fetched).
• msa_resolution_summary.json aggregates run-level MSA source counts and fetch/cache stats.
• template_resolution.json records which structural templates were attached to each chain.
• template_resolution_summary.json aggregates run-level template usage.
• missing_atoms.json is written when coordinates are missing and a fallback policy is used.

ipSAE (Interface Predicted Structural Alignment Error)

ProtenixScore computes ipSAE using the same definition as AF3Score's calculate_ipsae (inspired by the IPSAE script family), but using Protenix's token_pair_pae from full_confidence.json instead of AlphaFold JSON outputs.

Definition (directional, chain1 -> chain2):

• Let PAE(i,j) be the token-pair PAE from chain1 token i to chain2 token j.
• Keep only "valid" interface pairs where PAE(i,j) < pae_cutoff (default 10.0 Angstrom).
• For each chain1 token i, compute n0res(i) = count_j valid(i,j).
• Compute a TM-score-like normalization per token: d0(i) = max(1.0, 1.24 * cbrt(max(27, n0res(i)) - 15) - 1.8).
• Convert PAE to a PTM-like score: ptm(i,j) = 1 / (1 + (PAE(i,j) / d0(i))^2).
• Per-token ipSAE is the mean ptm(i,j) over valid j (0 if no valid pairs).
• Final ipSAE for the directional chain pair is max_i per_token_ipSAE(i).

Outputs:

• summary_confidence.json includes:
  • ipsae_by_chain_pair: map of directional chain-pair scores, keyed by source chain IDs (e.g. A_B, B_A).
  • ipsae_target_to_binder, ipsae_binder_to_target, ipsae_interface_max when --target_chains is provided.
• summary.csv includes ipsae_interface_max, ipsae_target_to_binder, ipsae_binder_to_target.

Which ipSAE metric should you use?

• For the common "many binders vs one target" setup (you pass --target_chains A), the binder-focused score is ipsae_binder_to_target (direction: binder -> target).

Common options

• --model_name (default: protenix-v2; pass protenix_base_default_v1.0.0 to opt into v1)
• --checkpoint_dir (optional, overrides default checkpoint location)
• --device (cpu|cuda:N|auto, default: auto)
• --dtype (fp32|bf16|fp16, default: bf16)
• --use_msas (both|target|binder|false, default: false)
• --use_template (auto|true|false, default: true; auto enables templates when --template_map_csv has entries)
• --template_map_csv (optional; CSV map for structural templates)
• --template_missing_policy (ignore|error, default: ignore)
• --msa_map_csv (optional; CSV map for chain/sequence-provided MSAs)
• --target_msa_shared_dir / --binder_msa_shared_dir (optional shared MSA dirs by role)
• --msa_provider (mmseqs2|none, default: mmseqs2)
• --msa_host_url (default: https://api.colabfold.com)
• --msa_cache_mode (readwrite|read|write|none, default: readwrite)
• --msa_cache_dir (optional; defaults to <output>/msa_cache when cache mode is not none)
• --msa_missing_policy (error|single, default: error)
• --validate_msa_inputs (true|false, default: true)
• --chain_sequence (optional; override chain sequences, format A=SEQUENCE, repeatable)
• --target_chains (optional; comma-separated chain IDs to treat as target)
• --target_chain_sequences (optional; FASTA of target sequences to match by sequence)
• --msa_use_env / --msa_use_filter (MMseqs2/ColabFold controls, default true)
• --msa_cache_refresh (force re-fetch when fetching into cache/write paths)
• --use_esm (optional)
• --convert_pdb_to_cif (always on for PDB input)
• --missing_atom_policy (reference|zero|error, default: reference)
• --max_tokens / --max_atoms (optional safety caps)
• --write_ipsae (true/false, default: true)
• --ipsae_pae_cutoff (default: 10.0 Angstrom)

How it works (high level)

1. Parse PDB/CIF (PDB is always converted to CIF).
2. Extract per-chain sequences from coordinates (or override via --chain_sequence).
3. Resolve structural templates and optional MSAs.
4. Build Protenix features from CIF.
5. Map source atom coordinates to Protenix atom ordering.
6. Run Protenix confidence head with the provided coordinates.

Structural template handling

The cytokineking Protenix fork accepts task-level structural templates in input JSON. ProtenixScore injects those templates before running the score-only confidence head. Protenix does not need to run diffusion to predict a structure, because the candidate coordinates are already provided. In score-only mode, structural templates are not used to generate coordinates; they are additional features for the confidence head while it scores the supplied target, binder, or whole complex.

Template map CSV columns:

• match selectors: sample_id (or sample), chain_id, sequence, role
• location: exactly one of template_path, path, cif, or pdb
• optional template_chain_id (or template_id / templateChainId)

Matching priority is deterministic:

1. exact sample_id + chain_id
2. role + sequence
3. sequence

Example:

sample_id,chain_id,role,template_path,template_chain_id
complex_0001,H,binder,/data/templates/vhh_framework.cif,A
complex_0001,A,target,/data/templates/target.cif,A

See examples/template_map_template.csv for a minimal file.

Template-aware scoring without MSAs:

python -m protenixscore score \
  --input ./ranked \
  --output ./scores_template \
  --recursive \
  --template_map_csv ./template_map.csv \
  --target_chains A

Template use is enabled by default. Pass --use_template false only for plain score-only runs that should ignore structural-template inputs.

Optional MSA handling

MSAs are optional. The default is --use_msas false, which keeps every chain single-sequence and avoids MSA fetch/cache overhead. This is the recommended default when structural templates are supplied for the scored structure or complex. Enable MSAs only when you want to test whether evolutionary signal adds predictive value for a target class.

Use --use_msas to control which roles get real MSAs:

• both: target and binder chains use real MSAs.
• target: only target chains use real MSAs, binders are single-sequence.
• binder: only binder chains use real MSAs, targets are single-sequence.
• false: all chains use single-sequence inputs.

Resolution order for enabled roles is deterministic:

1. --msa_map_csv exact sample_id + chain_id.
2. --msa_map_csv role + sequence.
3. --msa_map_csv sequence (must be unique).
4. shared role directory (--target_msa_shared_dir / --binder_msa_shared_dir).
5. cache (--msa_cache_dir) according to --msa_cache_mode.
6. fetch from provider (--msa_provider mmseqs2).
7. unresolved -> --msa_missing_policy (error by default).

If --msa_provider none is set, unresolved enabled-role chains still obey --msa_missing_policy (error fails fast, single falls back to single-sequence). --msa_provider none still reads existing mmseqs2 cache entries in read/readwrite modes.

Ambiguous map lookups are hard errors.

MSA map CSV

Supported columns:

• match selectors: sample_id (or sample), chain_id, sequence, role
• location: msa_dir OR (pairing_path + non_pairing_path)

Rules:

• At least one selector strategy is required: sample_id+chain_id and/or sequence.
• Duplicate keys are hard errors (sample_id+chain_id, role+sequence, sequence-only).
• sample_id is normalized using the same sample sanitizer as scoring.
• sequence matching normalizes by uppercasing and removing spaces/gaps.

Template:

sample_id,chain_id,role,msa_dir
complex_0001,A,target,/data/msa/complex_0001_A
complex_0001,H,binder,/data/msa/complex_0001_H

Sequence-level reuse:

role,sequence,msa_dir
target,EVQLVESGGGLVQPGGSLRLS...,/data/msa/target_shared_1
binder,QVQLQQSGAELVKPGASVK...,/data/msa/binder_shared_heavy_chain

Target/binder batch workflow

If you are scoring many binders against a fixed target:

python -m protenixscore score \
  --input ./ranked \
  --output ./scores \
  --recursive \
  --target_chains A \
  --template_map_csv ./template_map.csv

Notes:

• MSAs are off by default.
• Templates can be supplied for the target, binder, or both chains. For BindCraft/AF2-family structures, mapping both chains to the derived complex is a useful cross-validation scoring mode.
• If a target MSA is worth testing, add --use_msas target plus a shared/cache source for the target chain.

If you have explicit per-chain mappings, use --msa_map_csv:

python -m protenixscore score \
  --input ./ranked \
  --output ./scores \
  --recursive \
  --use_msas target \
  --target_chains A \
  --msa_map_csv ./examples/msa_map_template.csv

Troubleshooting

• If you see missing atom warnings, consider switching --missing_atom_policy to error to fail fast.
• If you hit device issues, try --device cpu to verify your setup.
• If checkpoints are not found, specify --checkpoint_dir.