Great summary! Apart from James and Mark's caveats about experimental structures being biased toward low-energy conformations, there's also the basic fact that every "experimental" structure is also a model and that even the PDB contains models with error - ill-defined or missing densities, extra (or unnecessary) water molecules, ligands with strain, etc. Also, out of the 200K PDB structures, only about 2oK have co-crystallized ligands. That's not a very small number, but I think it's a major reason why AF, while trained on the PDB and otherwise working well, works less well on predicting small molecule interactions which are still the bottleneck for structure-based design.
Great summary! Apart from James and Mark's caveats about experimental structures being biased toward low-energy conformations, there's also the basic fact that every "experimental" structure is also a model and that even the PDB contains models with error - ill-defined or missing densities, extra (or unnecessary) water molecules, ligands with strain, etc. Also, out of the 200K PDB structures, only about 2oK have co-crystallized ligands. That's not a very small number, but I think it's a major reason why AF, while trained on the PDB and otherwise working well, works less well on predicting small molecule interactions which are still the bottleneck for structure-based design.