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license: mit
tags:
- biology
- protein
- drug-target-interaction
- mitochondria
- apoptosis
- binding-affinity
- esm2
- chemberta
datasets:
- jglaser/binding_affinity
metrics:
- pearsonr
- spearmanr
- rmse
- mae
---
# MitoInteract: Protein-Molecule Binding Affinity Prediction for Mitochondrial Apoptosis Research
## Overview
MitoInteract is a dual-encoder model that predicts **binding affinity (pKd)** between any protein and any molecule.
It combines:
- **ESM-2 650M** (protein encoder) for protein sequence understanding
- **ChemBERTa** (molecule encoder) for SMILES-based molecular representation
- **Bidirectional cross-attention** fusion layer
- **4-layer MLP** regression head
## Intended Use
This model is designed for **mitochondrial apoptosis research**, enabling researchers to:
- Predict how ceramides interact with mitochondrial membrane proteins (VDAC1, VDAC2)
- Screen BCL-2 family protein interactions with BH3 mimetic drugs (venetoclax, navitoclax, ABT-737)
- Explore protein-lipid interactions in the apoptosis pathway
- Run in-silico binding experiments before wet-lab validation
## Quick Start
```python
from model import load_model, predict_binding
# Load model
model, config = load_model("full_model.pt", device="cuda")
# Predict ceramide C16 binding to VDAC1
result = predict_binding(
model,
protein_seq="MPPYLTFGLKAGALLPLTLPYVRAEAVTKLKLTLNAFEGASK...", # VDAC1
smiles="CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)/C=C/CCCCCCCCCCCCC", # Ceramide C16
device="cuda"
)
print(f"Predicted pKd: {result['pKd']:.3f}")
print(f"Predicted Kd: {result['Kd_uM']:.3f} µM")
```
## Key Apoptosis Targets
| Protein | Role in Apoptosis |
|---------|-------------------|
| BCL-2 | Anti-apoptotic, prevents MOMP |
| BCL-XL | Anti-apoptotic, sequesters BAX/BAK |
| BAX | Pro-apoptotic, forms pores in outer membrane |
| BAK | Pro-apoptotic, oligomerizes in membrane |
| VDAC1 | Voltage-dependent anion channel, ceramide target |
| Cytochrome c | Released during MOMP, activates caspase cascade |
## Key Molecules
| Molecule | Role |
|----------|------|
| Ceramide C16 | Lipid mediator, promotes MOMP via VDAC |
| Ceramide C2 | Short-chain ceramide analog |
| Venetoclax | BCL-2 inhibitor (FDA-approved) |
| Navitoclax | BCL-2/BCL-XL dual inhibitor |
| ABT-737 | BCL-2/BCL-XL/BCL-w inhibitor |
| Cardiolipin | Mitochondrial inner membrane lipid |
## Training Details
- **Dataset**: jglaser/binding_affinity (1.9M protein-ligand pairs)
- **Architecture**: ESM-2 650M (frozen) + ChemBERTa (frozen) + Cross-Attention + MLP
- **Training**: AdamW, lr=1e-3, cosine schedule, early stopping
- **Best Validation Pearson R**: -0.9107
## Citation
Based on:
- BAPULM (arxiv:2411.04150) - frozen encoder + MLP pattern
- SSM-DTA (arxiv:2206.09818) - CLS cross-attention fusion
- ESM-2 (arxiv:2202.03555) - protein language model
- ChemBERTa (arxiv:2010.09885) - molecular language model
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