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protein_sequence_similarity_search

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Find homologous protein sequences from a query sequence using MMseqs2 (fast, ColabFold web API) or BLAST (comprehensive, EBI). Use when the user provides a protein sequence or FASTA file and wants homologs, function inference by sequence similarity, or input for an MSA. Do NOT use for structural similarity (use foldseek) or DNA/RNA queries.

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Protein Sequence Similarity Search

Overview

Two complementary search engines, each wrapped as a submit-poll-download-parse pipeline:

  • MMseqs2 (ColabFold) — fast, default. Searches UniRef (+ optional MGnify environmental). Best for quickly building an MSA-grade hit set.
  • EBI BLAST (NCBI BLAST hosted at EBI) — slower but more exhaustive search across multiple UniProt/UniRef/PDB databases. Use when you need BLAST-specific scoring (e.g., comparing against a published BLAST result) or when MMseqs2 returns few hits.

Both tools save the full hit list to a JSON file on disk and return only a top-10 markdown preview in the response, keeping the agent's context window small.

Project Tools (VenusFactory2)

ToolArgsReturnsDescription
download_mmseqs2_homologs_by_sequencesequence_or_fasta_path (required, raw sequence or FASTA file path), out_dir (required), include_mgnify (default False), poll_interval (default 10.0 s), timeout_secs (default 900 s)JSON: {status, file_info {file_path -> mmseqs2_<ticket>.json, file_size, format: "json"}, content_preview (top-10 markdown table), biological_metadata {engine, ticket_id, query_length, hit_count, include_mgnify}}Fast UniRef homologue search via ColabFold MMseqs2 API.
download_blast_homologs_by_sequencesequence_or_fasta_path (required), out_dir (required), database (default "uniprotkb_swissprot"; comma-separated list ok), email (optional, falls back to env USER_EMAIL), poll_interval (default 30.0 s), timeout_secs (default 900 s)JSON: {status, file_info {file_path -> blast_<jobid>.json}, content_preview, biological_metadata {engine, job_id, query_length, databases, hit_count, email}}Authoritative BLAST search against UniProt/UniRef/PDB at EBI.

When to Use This Skill

  • The user gives a sequence and asks "find similar proteins" / "what's this protein's family" / "find homologs"
  • You need to build an MSA from a single seed sequence: run MMseqs2 → write hits → download_clustalo_msa_by_fasta
  • You need orthologs in a specific clade: BLAST with database=uniprotkb_human (or _bacteria, _viruses, etc.)
  • You need PDB hits to seed structure-based analysis: BLAST with database=pdb

Which Engine to Pick

SituationEngine
Default / unspecifiedMMseqs2 (faster, ~1-3 min)
User explicitly says "BLAST"BLAST
MMseqs2 returned <5 hitsBLAST fallback
Need PDB-only hitsBLAST with database=pdb
Need MGnify environmental hitsMMseqs2 with include_mgnify=True
Want comprehensive UniProtKB+TrEMBL coverageBLAST with database=uniprotkb

Supported BLAST Databases

uniprotkb uniprotkb_swissprot uniprotkb_swissprotsv uniprotkb_reference_proteomes uniprotkb_trembl uniprotkb_refprotswissprot uniprotkb_archaea uniprotkb_arthropoda uniprotkb_bacteria uniprotkb_complete_microbial_proteomes uniprotkb_eukaryota uniprotkb_fungi uniprotkb_human uniprotkb_mammals uniprotkb_nematoda uniprotkb_rodents uniprotkb_vertebrates uniprotkb_viridiplantae uniprotkb_viruses uniprotkb_enzyme uniprotkb_covid19 uniref100 uniref90 uniref50 pdb

Output JSON Schema (file_info.file_path)

{
  "hits": [
    {"target_id": "...", "q_cov": 78.3, "e_value": 1.2e-50, "identity": 0.45, "aln_len": 240, ...},
    ...
  ],
  "metadata": {"engine": "MMseqs2 (ColabFold)", "ticket_id": "...", "query_length": 256, "hit_count": 178, ...}
}

Rate Limiting

  • ColabFold MMseqs2: 2 req/s, ~1-3 min wall clock per job. Polls every 10 s.
  • EBI BLAST: 2 req/s submit; polls every 30 s. Jobs take 2-10 min.
  • Both timeout at 15 min by default — increase timeout_secs for very large queries.

Common Mistakes

  • Passing a FASTA file with multiple records but expecting all to be searched: only the first record is used. Loop in the agent if you need multiple queries.
  • Skipping out_dir: required. Tools error with ValidationError: empty out_dir.
  • Setting database to an unsupported value: returns ValidationError with the full allowed list — pick from that list.
  • Treating MMseqs2 hits as the final answer when count is 0: this is a soft failure; fall back to BLAST.

References