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GraphDTA with ESM-2 and Cross-Attention

📌 Project Overview

This repository contains an advanced Deep Learning model for Drug-Target Affinity (DTA) prediction. The model integrates Graph Neural Networks (GAT) for molecular representation and ESM-2 (Evolutionary Scale Modeling) for protein sequence embeddings, fused via a Bi-Directional Cross-Attention mechanism.

The goal is to accurately predict the binding affinity between a drug molecule (SMILES) and a target protein sequence, addressing the cold-start problem (unseen drugs/targets) in drug discovery.

🚀 Key Features

  • Protein Encoder: Utilizes ESM-2 (650M parameter) pre-trained protein language model for rich sequence representations.
  • Drug Encoder: Graph Attention Network (GAT) to capture structural information of drug molecules.
  • Attention Mechanism: Bi-Directional Cross-Attention (Drug-to-Protein & Protein-to-Drug) to model specific molecular interactions.
  • Robust Evaluation: Implements Cold-Drug and Cold-Target generic splits to test generalization capabilities.
  • Metrics: Evaluated using MDSE (Mean Squared Error) and CI (Concordance Index).

📊 Performance

  • MSE: ~0.46
  • Concordance Index (CI): ~0.79

🔗 References

  • ESM-2: Lin et al., "Language models of protein sequences at the scale of evolution to structure optimization", 2022.
  • GraphDTA: Nguyen et al., "GraphDTA: Predicting drug–target binding affinity with graph neural networks", 2021.

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