AlphaFold 3 can rapidly reduce a vast search space in a way physically-based methods alone cannot. This narrowly focused search space allows scientists to apply their rigorous, explainable, physical methods, which are slow and expensive, to a small set of promising alternatives. This accelerates drug discovery and uncovers insights that would otherwise be too costly or time-consuming.

The future of science isn't about AI versus traditional methods, but about their intelligent integration.

My only worry is that AlphaFold and others, e.g. ESM, seem to be bit fragile for out-of-distribution sequences. They are not doing a great job with unusual sequences, at least in my experience. But hopefully they will improve and provide better uncertainty measures.

It’s actually required as part of the submission for FDA approval that you posit a specific Mechanism of Action for why your drug works the way it does. You can’t get approval without it

Vioxx is a nice example of a molecule that got all the way to large-scale deployment before being taken off the market for side effects that were known. Only a decade before that, I saw a very proud pharma scientist explaining their "mechanism of action" for vioxx, which was completely wrong.