PPI Interface Analysis Pipeline

Protein-protein interface hotspot prediction using computational alanine scanning and SASA-based BSA analysis.

Method

Mode A — Interface Analysis (CPU, fast) Given a PDB file, computes:

• Interface residues via BSA (buried surface area) differential
• Contact map (Cα-Cα < 8Å, heavy atom < 5Å)
• Computational alanine scanning with hotspot scoring
• Shape complementarity proxy
• Polar/hydrophobic/charged composition

Demo: PD-1/PD-L1 immune checkpoint complex (PDB: 4ZQK) — a key cancer immunotherapy target.

Results Summary

Metric	Value
Total BSA	1823.7 Ų (typical Ab-Ag: 1200–2000 Ų)
Shape Complementarity	0.666 (good, >0.65)
Chain A (PD-L1) hotspots	12 residues
Chain B (PD-1) hotspots	10 residues

Top hotspots: B134ILE, A56TYR, A125ARG, B128LEU, A113ARG

Usage

pip install biopython numpy pandas matplotlib seaborn scipy requests

python ppi_pipeline.py

Output Files

• interface_residues.csv — all interface residues with BSA and hotspot scores
• hotspots.json — hotspot list for downstream binder design
• interface_bsa.png — BSA bar chart
• contact_map.png — inter-chain contact heatmap
• composition_radar.png — polar/apolar composition radar

References

• Bogan & Thorn (1998). Anatomy of hot spots in protein interfaces. JMB
• Mirdita et al. (2022). ColabFold: making protein folding accessible to all. Nature Methods