AlphaFold2 Structure Validation Skill

AlphaFold2 Structure Validation

Prerequisites

| Requirement | Minimum | Recommended | |-------------|---------|-------------| | Python | 3.8+ | 3.10 | | CUDA | 11.0+ | 12.0+ | | GPU VRAM | 32GB | 40GB (A100) | | RAM | 32GB | 64GB | | Disk | 100GB | 500GB (for databases) |

How to run

First time? See Installation Guide to set up Modal and biomodals.

Option 1: ColabFold (recommended for multimer)

cd biomodals
modal run modal_colabfold.py \
  --input-faa sequences.fasta \
  --out-dir output/

GPU: A100 (40GB) | Timeout: 3600s default

Option 2: Local installation

git clone https://github.com/deepmind/alphafold.git
cd alphafold

python run_alphafold.py \
  --fasta_paths=query.fasta \
  --output_dir=output/ \
  --model_preset=monomer \
  --max_template_date=2026-01-01

Option 3: ESMFold (fast single-chain)

modal run modal_esmfold.py \
  --sequence "MKTAYIAKQRQISFVK..."

Key parameters

| Parameter | Default | Options | Description | |-----------|---------|---------|-------------| | --model_preset | monomer | monomer/multimer | Model type | | --num_recycle | 3 | 1-20 | Recycling iterations | | --max_template_date | - | YYYY-MM-DD | Template cutoff | | --use_templates | True | True/False | Use template search |

Output format

output/
├── ranked_0.pdb           # Best model
├── ranked_1.pdb           # Second best
├── ranking_debug.json     # Confidence scores
├── result_model_1.pkl     # Full results
├── msas/                  # MSA files
└── features.pkl           # Input features

Extracting metrics

import pickle

with open('result_model_1.pkl', 'rb') as f:
    result = pickle.load(f)

plddt = result['plddt']
ptm = result['ptm']
iptm = result.get('iptm', None)  # Multimer only
pae = result['predicted_aligned_error']

Sample output

Successful run

$ python run_alphafold.py --fasta_paths complex.fasta --model_preset multimer
[INFO] Running MSA search...
[INFO] Running model 1/5...
[INFO] Running model 5/5...
[INFO] Relaxing structures...

Results:
  ranked_0.pdb:
    pLDDT: 87.3 (mean)
    pTM: 0.78
    ipTM: 0.62
    PAE (interface): 8.5

Saved to output/

What good output looks like:

pLDDT: > 85 (mean, on 0-100 scale) or > 0.85 (normalized)
pTM: > 0.70
ipTM: > 0.50 for complexes
PAE_interface: < 10

Decision tree

Should I use AlphaFold?
│
├─ What are you predicting?
│  ├─ Single protein → ESMFold (faster)
│  ├─ Protein-protein complex → AlphaFold/ColabFold ✓
│  ├─ Protein + ligand → Chai or Boltz
│  └─ Batch of sequences → ColabFold ✓
│
├─ What do you need?
│  ├─ Highest accuracy → AlphaFold/ColabFold ✓
│  ├─ Fast screening → ESMFold
│  └─ MSA-free prediction → Chai or ESMFold
│
└─ Which AF2 option?
   ├─ Local installation → Full control, slow setup
   ├─ ColabFold → Easier, MSA server
   └─ Modal → Recommended for batch

Typical performance

| Campaign Size | Time (A100) | Cost (Modal) | Notes | |---------------|-------------|--------------|-------| | 100 complexes | 1-2h | ~$8 | With MSA server | | 500 complexes | 5-10h | ~$40 | Standard campaign | | 1000 complexes | 10-20h | ~$80 | Large campaign |

Per-complex: ~30-60s with MSA server.

Verify

find output -name "ranked_0.pdb" | wc -l  # Should match input count

Troubleshooting

Low pLDDT regions: May indicate disorder or poor design Low ipTM: Interface not confident, check hotspots High PAE off-diagonal: Chains may not interact OOM errors: Use ColabFold with MSA server instead

Error interpretation

| Error | Cause | Fix | |-------|-------|-----| | RuntimeError: CUDA out of memory | Sequence too long | Use A100 or split prediction | | KeyError: 'iptm' | Running monomer on complex | Use multimer preset | | FileNotFoundError: database | Missing MSA databases | Use ColabFold MSA server | | TimeoutError | MSA search slow | Reduce num_recycles |

Next: protein-qc for filtering and ranking.

Agent Skills: AlphaFold2 Structure Validation

Install this agent skill to your local

Skill Files