adaptyvbio/campaign-manager

Campaign Manager

Goal-oriented design

From goal to pipeline

When user says: "I need 10 good binders for EGFR"

Campaign Planning:

Goal: 10 high-quality binders for EGFR
├── Achievable: Yes (standard target)
├── Recommended pipeline: rfdiffusion → proteinmpnn → chai → protein-qc
├── Estimated designs needed: 500 backbones (to get ~50 passing QC)
├── Estimated time: 8-12 hours total
├── Estimated cost: ~$60 (Modal GPU compute)
└── Expected yield:
    ├── After backbone (500): 500 structures
    ├── After sequence (×8): 4,000 sequences
    ├── After validation: 4,000 predictions
    ├── After QC (~10-15%): 400-600 candidates
    └── After clustering: 10-20 diverse final designs

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Complete pipeline generator

Standard miniprotein binder campaign

# Step 1: Fetch and prepare target (5 min)
curl -o target.pdb "https://files.rcsb.org/download/{PDB_ID}.pdb"
# Trim to binding region if needed

# Step 2: Generate backbones (2-3h, ~$15)
# RFdiffusion runs from the official repo, not biomodals
python run_inference.py \
  inference.input_pdb=target.pdb \
  contigmap.contigs=[A1-150/0 70-100] \
  ppi.hotspot_res=[A45,A67,A89] \
  inference.num_designs=500

# Checkpoint: ls output/*.pdb | wc -l  # Should be 500

# Step 3: Design sequences (1-2h, ~$10)
for f in output/*.pdb; do
  modal run modal_ligandmpnn.py \
    --input-pdb "$f" \
    --params-str "--number_of_batches 8 --temperature 0.1"
done

# Checkpoint: grep -c "^>" output/seqs/*.fa  # Should be ~4000

# Step 4: Quick ESM2 filter (30 min, ~$5, optional)
modal run modal_esm2_predict_masked.py --input-faa output/all_seqs.fa
# Filter sequences with PLL < 0.0

# Step 5: Structure validation (3-4h, ~$35)
modal run modal_alphafold.py \
  --input-faa output/filtered_seqs.fa \
  --out-dir predictions/

# Checkpoint: find predictions -name "*rank_001.pdb" | wc -l

# Step 6: Filter and rank (protein-qc skill)
# Apply thresholds: pLDDT > 0.85, ipTM > 0.5, scRMSD < 2.0
# Compute composite score
# Cluster at 70% identity, select top from each cluster

Total estimated time: 8-12 hours Total estimated cost: ~$60-70

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Campaign size recommendations

| Goal | Backbones | Sequences/BB | Total Seq | Expected Passing | |------|-----------|--------------|-----------|------------------| | 5 binders | 200 | 8 | 1,600 | 160-240 | | 10 binders | 500 | 8 | 4,000 | 400-600 | | 20 binders | 1,000 | 8 | 8,000 | 800-1,200 | | 50 binders | 2,500 | 8 | 20,000 | 2,000-3,000 |

Rule of thumb: Generate 50x more designs than you need (10-15% pass rate × clustering).

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Tool selection guide

When to use each tool

| Scenario | Recommended Tool | Reason | |----------|------------------|--------| | Standard miniprotein | RFdiffusion + ProteinMPNN | High diversity, proven | | Need higher success rate | BindCraft | Integrated design loop | | All-atom precision needed | BoltzGen | Side-chain aware | | Difficult target | Mosaic | Gradient, multi-model objective | | Need fast iteration | ESMFold2 + ESM2 | Quick screening |

Target difficulty assessment

| Indicator | Easy Target | Difficult Target | |-----------|-------------|------------------| | Surface type | Concave pocket | Flat or convex | | Conservation | High | Low | | Known binders | Yes | No | | Flexibility | Rigid | Flexible | | Expected pass rate | 15-20% | 5-10% |

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Campaign health assessment

Quick metrics check

import pandas as pd

def assess_campaign(csv_path):
    df = pd.read_csv(csv_path)

    # Calculate pass rates
    plddt_pass = (df['pLDDT'] > 0.85).mean()
    iptm_pass = (df['ipTM'] > 0.50).mean()
    scrmsd_pass = (df['scRMSD'] < 2.0).mean()
    all_pass = ((df['pLDDT'] > 0.85) & (df['ipTM'] > 0.5) & (df['scRMSD'] < 2.0)).mean()

    # Determine health
    if all_pass > 0.15:
        health = "EXCELLENT"
    elif all_pass > 0.10:
        health = "GOOD"
    elif all_pass > 0.05:
        health = "MARGINAL"
    else:
        health = "POOR"

    # Identify top issue
    issues = []
    if plddt_pass < 0.20:
        issues.append("Low pLDDT - backbone or sequence issue")
    if iptm_pass < 0.20:
        issues.append("Low ipTM - hotspot or interface issue")
    if scrmsd_pass < 0.50:
        issues.append("High scRMSD - sequence doesn't specify backbone")

    return {
        "health": health,
        "overall_pass_rate": all_pass,
        "plddt_pass_rate": plddt_pass,
        "iptm_pass_rate": iptm_pass,
        "scrmsd_pass_rate": scrmsd_pass,
        "top_issues": issues
    }

Interpreting results

| Health | Pass Rate | Action | |--------|-----------|--------| | EXCELLENT | > 15% | Proceed to selection | | GOOD | 10-15% | Proceed, normal yield | | MARGINAL | 5-10% | Review failure tree | | POOR | < 5% | Diagnose and restart |

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Cost estimation

Per-tool costs (Modal)

| Tool | GPU | $/hour | Typical Job | Cost | |------|-----|--------|-------------|------| | RFdiffusion | A10G | ~$1.20 | 500 designs/2h | ~$2.50 | | ProteinMPNN | T4 | ~$0.60 | 4000 seq/1.5h | ~$1.00 | | ESM2 (PLL) | A10G | ~$1.20 | 4000 seq/30min | ~$0.60 | | AlphaFold | A100 | ~$4.50 | 4000 preds/4h | ~$18.00 | | Chai | A100 | ~$4.50 | 500 preds/1h | ~$4.50 |

Campaign cost estimates

| Campaign Size | Total Cost | Notes | |---------------|------------|-------| | Small (100 bb) | ~$15 | Quick exploration | | Standard (500 bb) | ~$60 | Most campaigns | | Large (1000 bb) | ~$120 | Comprehensive | | XL (5000 bb) | ~$600 | Very thorough |

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Pipeline variants

High-throughput (maximize diversity)

# More backbones, fewer sequences each (RFdiffusion from the official repo)
python run_inference.py inference.num_designs=2000
modal run modal_ligandmpnn.py --input-pdb bb.pdb --params-str "--number_of_batches 4 --temperature 0.2"

High-quality (maximize per-design quality)

# Fewer backbones, more sequences each, lower temperature
python run_inference.py inference.num_designs=200
modal run modal_ligandmpnn.py --input-pdb bb.pdb --params-str "--number_of_batches 32 --temperature 0.1"

Quick exploration (fast iteration)

# Small batch, ESMFold2 for fast single-sequence folding
# RFdiffusion runs from the official repo (not biomodals); see the rfdiffusion skill
modal run modal_ligandmpnn.py --input-pdb bb.pdb --params-str "--number_of_batches 8"
modal run modal_esmfold2.py --input-faa all_seqs.fa

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See also

• Tool-specific parameters: rfdiffusion, proteinmpnn, mosaic, chai, boltz, alphafold
• QC thresholds and filtering: protein-qc
• Tool selection guidance: binder-design