foldseek

name	foldseek
description	Structure similarity search with Foldseek. Use this skill when: (1) Finding similar structures in PDB/AFDB databases, (2) Structural homology search, (3) Database queries by 3D structure, (4) Finding remote homologs not detected by sequence, (5) Clustering structures by similarity. For sequence similarity, use uniprot BLAST. For structure prediction, use chai or boltz.
license	MIT
category	utilities
tags	["search","structure","database","similarity"]
source	https://github.com/adaptyvbio/protein-design-skills

Foldseek Structure Search

Prerequisites

Requirement	Minimum	Recommended
RAM	8GB	16GB
Disk	10GB	50GB (local databases)

No GPU required.

How to run

Option 1: Web Server (Quick, rate-limited)

curl -X POST "https://search.foldseek.com/api/ticket" \
  -F "q=@query.pdb" \
  -F "database[]=afdb50" \
  -F "database[]=pdb100"

Option 2: Local installation

conda install -c conda-forge -c bioconda foldseek

# Search PDB
foldseek easy-search query.pdb /path/to/pdb100 results.m8 tmp/

# Search AlphaFold DB
foldseek easy-search query.pdb /path/to/afdb50 results.m8 tmp/

Key Parameters

Parameter	Default	Description
--min-seq-id	0.0	Minimum sequence identity
-e	0.001	E-value threshold
--alignment-type	2	0=3Di, 1=TM, 2=3Di+AA

Databases

Database	Description	Size
pdb100	PDB clustered at 100%	~200K structures
afdb50	AlphaFold DB at 50%	~67M structures
swissprot	SwissProt structures	~500K structures

Common Use Cases

Novelty check

foldseek easy-search design.pdb afdb50 novelty.m8 tmp/
# Novel if: top hit identity < 30%

Find similar natural structures

foldseek easy-search design.pdb pdb100 similar_natural.m8 tmp/

Scaffold search for motif grafting

foldseek easy-search motif.pdb pdb100 scaffolds.m8 tmp/ \
  --min-seq-id 0.0 -e 10

Decision Tree

Searching by?
├─ 3D structure → Foldseek ✓
├─ Sequence → Use BLAST (uniprot skill)
└─ Both → Run both, compare results

Troubleshooting

Error	Cause	Fix
No hits	Too strict cutoff	Lower e-value, try larger database
Database not found	Wrong path	Check database location
Out of memory	Large database	Use web server

Next: Download hits with pdb skill → use for scaffold design.