Most AlphaFold pockets look ligand-bound, and that bias measurably changes pocket detection and docking success
- Each predicted AlphaFold pocket across a large set of proteins was positioned between the unbound (apo) and ligand-bound (holo) states seen in experimental structures of the same site.
- Most pockets resembled the holo state, mirroring the balance of experimental structures in the PDB.
- In a retrospective analysis, binding-site predictors and cognate-ligand docking performed better on holo-like pockets, especially where apo and holo states differ strongly. The confidence score reflects pocket variability, not state.
- Per-pocket classifications are released to guide docking readiness.
💡 Points Based on the abstract
AlphaFold-based docking benchmarks may partly reward PDB bias rather than prediction skill, since most predicted pockets sit on the holo side. That makes the released per-pocket labels a handy triage step before docking into a model. The analysis is retrospective and cognate-ligand only, so behaviour with novel chemotypes remains an open question.
A tale of two states: AlphaFold binding pockets on the apo-holo continuum ↗