Alphafold was largely trained on the structures in the Protein Data Bank, which includes lots of important protein targets. Just by virtue of evolutionary biolo

Alphafold was largely trained on the structures in the Protein Data Bank, which includes lots of important protein targets. Just by virtue of evolutionary biology, many proteins are variants of one another, so if you're doing something like running AF on all of the proteins in the human body (only 24k or so), you're including lots of targets that were part of the training set, lots of targets that are closely related, and lots of targets we don't have structures for. Many (most?) proteins are also dynamic, so can't really be represented well by a single structure (rotating a sidechain inside a pocket when using a structure for virtual screening will frequently yield completely different 'hit' molecules, for instance). AF2 is a better guesser than previous tools for a reasonable structure, but that's like 1 step in a 47 step process to 'finding a new drug.' Even here, "AlphaFold" didn't find the drugs candidates, it generated the structure(s) that they ran common virtual screening tools on (which introduces all kinds of other assumptions and approximations depending on the tool).