To evolve AI from pattern matching to understanding physics for protein engineering, structural data is insufficient. Models need physical parameters like Gibbs free energy (delta-G), obtainable from affinity measurements, to become truly predictive and transformative for therapeutic development.

Current AI models for science are narrow surrogates for specific tasks. The grand vision is to build a foundation model for physics that understands a wide range of coupled, multi-physics phenomena. This single model could be used for simulation, inverse design, and control across many scientific and engineering domains.

A classical, bottom-up simulation of a cell is infeasible, according to John Jumper. He sees the more practical path forward as fusing specialized models like AlphaFold with the broad reasoning of LLMs to create hybrid systems that understand biology.

Future progress in biology requires moving beyond static models. The new paradigm involves an AI that reasons over hypotheses, prioritizes experiments, learns from the empirical outcomes, and updates its internal world model. This creates a scalable, closed-loop system for scientific discovery.

While traditional hybrid models still require solving differential equations during use, Physics-Informed Neural Networks (PINNs) learn the final outcome directly. They are trained to obey physical laws but don't need the equations for inference. This provides a significant speed advantage for computationally expensive systems like chromatography, making them more suitable for real-time applications.

Michael Antonov argues against a pure AI approach. He envisions a future where hundreds of different models—statistical AI, precise molecular dynamics, and scalable coarse-grained models—are stacked together to simulate biological processes at different scales, bridging their individual gaps.

To ensure scientific validity and mitigate the risk of AI hallucinations, a hybrid approach is most effective. By combining AI's pattern-matching capabilities with traditional physics-based simulation methods, researchers can create a feedback loop where one system validates the other, increasing confidence in the final results.

Biohub applies mechanistic interpretability to its protein language models. By analyzing the model's internal representations—learned from both known and unknown biology—researchers can uncover emergent biological principles. This turns the model from a black box predictor into an engine for scientific discovery itself.

Traditional science failed to create equations for complex biological systems because biology is too "bespoke." AI succeeds by discerning patterns from vast datasets, effectively serving as the "language" for modeling biology, much like mathematics is the language of physics.