AlphaFold troubleshooting

When AlphaFold Fetch fails or returns something unexpected, this page covers the common failure modes — from "structure not found" and invalid UniProt IDs to low-confidence regions, EBI availability errors, and the monomer-without-ligands nature of the result.

Troubleshooting

"Structure not found in AlphaFold Database"

The most common failure mode. The protein you asked for is not in the database.

Common causes:

• The UniProt entry is from an organism not covered by the AlphaFold DB campaign
• The accession is unreviewed (TrEMBL) and was not included in the bulk run
• The entry is a fragment, peptide, or non-standard record

Recovery:

1. Easiest — switch to ESMFold: "Predict the structure with ESMFold using the UniProt sequence". The platform will fetch the sequence and run ESMFold.
2. Fallback in one request — ask "Try AlphaFold first; if it is not in the database, run ESMFold." The orchestrator chains both steps.
3. Manual check — visit https://alphafold.ebi.ac.uk/entry/{uniprot_id} to confirm the gap before re-running.

"Invalid UniProt ID"

The accession failed validation.

Common causes:

• Typo (UniProt accessions are case-sensitive — p00533 is invalid, P00533 is valid)
• You passed a gene symbol (EGFR) instead of an accession (P00533)
• You passed a PDB ID (6LU7) instead of a UniProt accession

Recovery: ask in chat "Find the UniProt accession for <name>" and re-run with the result.

Structure loaded but quality looks poor

The structure fetched fine, but large regions are red/orange in the 3D viewer (pLDDT < 70).

This is usually correct. AlphaFold legitimately reports low confidence for:

• Intrinsically disordered regions — flexible loops, signal peptides, transactivation domains
• Termini — N- and C-terminal regions often score below 50
• Linkers — flexible regions connecting structured domains

If the low-confidence regions matter for your downstream analysis (e.g. docking, binding-site work), focus on the high-confidence core domains and treat low-confidence regions as unreliable.

Network / availability errors

The fetch calls the EBI public endpoint at https://alphafold.ebi.ac.uk. If EBI is down or slow:

• Retry after 30–60 seconds — transient failures are common for any public API
• If persistent, switch to ESMFold — it runs on the platform's own GPUs and does not depend on EBI

Multiple AlphaFold versions

The AlphaFold DB has shipped several model versions, and its prediction API reports both the current one (latestVersion) and the full list (allVersions). The fetch returns the F1 entry for the accession at whatever version the API currently names — it does not hardcode one, because EBI deletes the old file keys on a version bump and a stale version 404s for every accession.

So the version you get can change between runs. Record modelVersion from the result alongside any figure you derive from the structure.

If you need a specific older version for reproducibility against a published paper, that's not something you can ask for: the fetch always takes the version the API currently names. Download that version manually from EBI.

Downstream tool says "PDB has no ligands / no chain B"

AlphaFold predictions are monomers without ligands. The PDB file has:

• A single chain (A)
• No bound ligands, ions, or cofactors
• No crystal-packing artifacts

For docking, this is what you want. For complex-aware analysis (e.g. studying a protein's native cofactor environment), ask for the PDB entry instead — experimental structures usually include ligands.

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