AlphaFold solved structure prediction — but structure isn't function

AlphaFold2 and its successors made structure prediction essentially a solved problem for single proteins in isolation. That's a genuine triumph, and it's reshaping drug discovery at speed. But I keep running into researchers who act as though the hard problem of protein biochemistry is now largely done. It isn't.

Structure tells you the shape of the molecule. It doesn't tell you how that shape changes as the protein moves through its conformational ensemble, how binding partners alter that ensemble, how post-translational modifications shift function, or what the protein does in the crowded, viscous, electrically charged environment of the actual cell. A protein structure database entry is a single frame from a film.

The independent researcher angle: most of the open problems in this space are computational and involve data that's publicly accessible. PDB files are free. Molecular dynamics simulation tools like OpenMM are open source. If you have a chemistry background and programming comfort, the barrier to doing real work here is much lower than it was a decade ago.

What are the questions you'd investigate if you had the structure of every human protein in hand? That's not a rhetorical question — I'm genuinely curious what directions people see.