Objective:

To explore the potential and limitations of AI in predicting antibody-antigen complexes for drug development, specifically addressing challenges in accuracy and reliability.

Key Findings:

• AI models like AlphaFold 3 and RFdiffusion have significantly advanced protein structure prediction and antibody discovery, but their performance on antibody-antigen complexes is less effective compared to other proteins.
• Benchmarking and comprehensive datasets like ABAG-docking are crucial for identifying gaps and guiding future research, highlighting the need for improved methodologies.

Interpretation:

AI has transformative potential in drug design but faces significant challenges in accurately predicting antibody-antigen interactions and providing reliable metrics, necessitating ongoing research.

Limitations:

• AI models may overfit to narrow datasets, leading to unreliable predictions, particularly in complex biological contexts.
• Confidence metrics can lack precision in distinguishing between accurate and misleading predictions, complicating decision-making in drug development.

Conclusion:

AI is revolutionizing biomolecular prediction and drug design, but ongoing improvements in model reliability, benchmarking, and confidence metrics are essential for maximizing its impact.