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foldseek
GitHub用于基于3D蛋白质结构进行相似性搜索的工具，支持PDB/AFDB数据库查询、结构同源比对及远程同源蛋白发现。适用于序列方法无法检测的结构相似性分析，需指定输入结构文件并选择本地或Web服务器运行方式。
Trigger Scenarios
寻找与给定蛋白质结构相似的3D构象
进行结构同源性搜索
通过3D结构查询数据库
发现序列相似度低但结构相似的同源蛋白
按结构相似性对蛋白质进行聚类
Install
npx skills add NeverSight/learn-skills.dev --skill foldseek -g -y
SKILL.md
Frontmatter
{
"name": "foldseek",
"tags": [
"search",
"structure",
"database",
"similarity"
],
"license": "MIT",
"category": "utilities",
"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.\nFor sequence similarity, use uniprot BLAST. For structure prediction, use chai or boltz.\n"
}
Foldseek Structure Search
Prerequisites
| Requirement | Minimum | Recommended |
|---|---|---|
| Python | 3.8+ | 3.10 |
| RAM | 8GB | 16GB |
| Disk | 10GB | 50GB (for local databases) |
How to run
Note: Foldseek can run locally or via web server. No GPU required.
Option 1: Web Server (Quick; rate-limited, use sparingly)
# Upload structure to web server
curl -X POST "https://search.foldseek.com/api/ticket" \
-F "q=@query.pdb" \
-F "database[]=afdb50" \
-F "database[]=pdb100"
Option 2: Local installation
# Install Foldseek
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/
Option 3: Python API
import subprocess
import pandas as pd
def foldseek_search(query_pdb, database, output="results.m8"):
"""Run Foldseek search."""
subprocess.run([
"foldseek", "easy-search",
query_pdb, database, output, "tmp/",
"--format-output", "query,target,pident,alnlen,evalue,bits"
])
return pd.read_csv(output, sep="\t",
names=["query", "target", "pident", "alnlen", "evalue", "bits"])
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 |
--max-seqs |
300 | Max hits to pass through prefilter; reducing this affects sensitivity |
Databases
| Database | Description | Size |
|---|---|---|
pdb100 |
PDB clustered at 100% | ~200K structures |
afdb50 |
AlphaFold DB at 50% | ~67M structures |
swissprot |
SwissProt structures | ~500K structures |
cath50 |
CATH domains | ~50K domains |
Output format
# results.m8 (tabular)
query target pident alnlen evalue bits
query 1abc_A 85.2 120 1e-45 180.5
query 2def_B 72.1 115 1e-32 145.2
Sample output
Successful run
$ foldseek easy-search query.pdb pdb100 results.m8 tmp/
[INFO] Loading database: pdb100 (194,527 entries)
[INFO] Searching...
[INFO] Found 127 hits
Top 5 hits:
1. 1abc_A - 85.2% identity, E=1e-45
2. 2def_B - 72.1% identity, E=1e-32
3. 3ghi_C - 68.5% identity, E=1e-28
4. 4jkl_A - 55.3% identity, E=1e-18
5. 5mno_B - 42.1% identity, E=1e-10
Decision tree
Should I use Foldseek?
│
├─ What are you searching?
│ ├─ By 3D structure → Foldseek ✓
│ ├─ By sequence → Use BLAST (uniprot skill)
│ └─ Both → Run both, compare results
│
└─ What do you need?
├─ Find structural homologs → Foldseek ✓
├─ Remote homolog detection → Foldseek ✓
├─ Structural clustering → Foldseek ✓
└─ Functional annotation → Cross-reference with UniProt
Common use cases
Find similar designs
# Compare your design to PDB
foldseek easy-search design.pdb pdb100 similar_natural.m8 tmp/
Novelty check
# Ensure design is novel (low similarity to known)
foldseek easy-search design.pdb afdb50 novelty.m8 tmp/
# Novel if: top hit identity < 30%
Scaffold search
# Find scaffolds for motif grafting
foldseek easy-search motif.pdb pdb100 scaffolds.m8 tmp/ \
--min-seq-id 0.0 -e 10
Verify
wc -l results.m8 # Number of hits
Troubleshooting
No hits: Lower e-value threshold, try larger database Too many hits: Increase min-seq-id threshold Slow search: Use smaller database
Error interpretation
| Error | Cause | Fix |
|---|---|---|
Database not found |
Wrong path | Check database location |
Invalid PDB |
Malformed structure | Validate PDB format |
Out of memory |
Large database | Use more RAM or web server |
Next: Download hits with pdb skill → use for scaffold design.
Version History
- e0220ca Current 2026-07-05 23:16
