Peptide Target Deorphanization

Deorphanize a peptide: given a peptide sequence plus an observed phenotype (and often a hypothesized target the peptide does NOT actually bind), find its likely real protein target(s) — using ToolUniverse's keyless characterization, homology, target-family, phenotype, cross-species, and (optional, key-gated) co-folding tools.

The target can be anything, not just a GPCR. A target-class router (GPCR ligand / ion-channel toxin / protease target / cytokine or growth-factor receptor / integrin ligand / antimicrobial / unknown) classifies the peptide up front and adapts the enumeration strategy. GPCRs are the best-trodden case (and the validated control), but the pipeline's spine — homology, motif, phenotype, cross-species, co-fold — is target-class-agnostic, and family enumeration uses HGNC gene-family (general) + InterPro (general) + GPCRdb (GPCR-only cross-check).

Core reasoning: LOOK UP, DON'T GUESS

The failure mode this skill defends against is guessing a target from the peptide's name or its assumed mechanism. A peptide can be phenotypically active yet not bind the hypothesized target — because it hits a paralog, a different family member, or the same receptor in a different species whose binding interface has diverged. So:

1. Never assert a target from memory. Every candidate must come from a tool result (homology hit, family enumeration, phenotype association, or structural co-fold), with the tool name and accession recorded.
2. Anchor on PHENOTYPE × STRUCTURE/SEQUENCE plausibility, not on the peptide's reputed mechanism. The real target is the intersection of (a) what the sequence/motif/structure says it could bind and (b) what the phenotype says is biologically relevant. A name-level guess ("it's a GLP-1 analog so it's GLP1R") is exactly what produces off-target errors.
3. Reconcile across species. "Binds in species A but not B" is usually interface sequence divergence, not a different target. Always pull the ortholog set and align the candidate receptor's ligand-binding interface across the assay species before concluding the peptide "doesn't work."
4. A non-binding result against the hypothesized target is a clue, not a dead end. It promotes the paralogs and phenotype-shared receptors to the top of the candidate list.

This skill is built on validated, mostly keyless tools (BLAST, ELM/PROSITE, GPCRdb/HGNC/GtoPdb, OpenTargets, EnsemblCompara/Alliance). The single key-gated step is the optional structural confirmation by co-folding (NVIDIA NIM), used only to rank an already-narrowed shortlist.