Find structural analogs

Best fit: search by structure — a structure goal.

The prompt

Fold the orphan GPCR GPR75 (UniProt: Q9ULV1) with ESMFold, then search for structural analogs using Foldseek against PDB and AlphaFold DB - which solved GPCR structures share the closest TM helix arrangement despite low sequence identity (<30%), and could their ligand binding sites inform GPR75 deorphanization screens?

What each tool contributes

• esmfold — folds the query sequence, so Foldseek has a structure to search with
• foldseek — 3D structure similarity search across PDB and AlphaFold DB using structural alphabet encoding
• blast — Sequence-based homology search for evolutionarily related proteins

Why these tools pair

Foldseek finds structural homologs via 3Di alphabet encoding while BLAST identifies sequence homologs — structural search catches remote homologs with <20% sequence identity that BLAST misses entirely, critical for finding druggable analogs of novel targets and identifying off-target selectivity risks

Data flow

Every tool operates on the same input: pdb_structure.

See also

• Sequence Analysis — the guided version: BLAST, ESMFold, and UniProt step by step.
• Which tool? — match a single goal to a tool.
• Workflows — every workflow and recipe.
• How the orchestrator picks tools — the same chain from a plain-language goal.