https://github.com/steineggerlab/folddisco
Fast indexing and search of discontinuous motifs in protein structures
https://github.com/steineggerlab/folddisco
bioinformatics foldseek motif protein-structure
Last synced: 6 months ago
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Fast indexing and search of discontinuous motifs in protein structures
- Host: GitHub
- URL: https://github.com/steineggerlab/folddisco
- Owner: steineggerlab
- License: gpl-3.0
- Created: 2023-02-21T05:02:01.000Z (over 2 years ago)
- Default Branch: master
- Last Pushed: 2025-02-19T13:00:45.000Z (8 months ago)
- Last Synced: 2025-02-19T14:22:03.383Z (8 months ago)
- Topics: bioinformatics, foldseek, motif, protein-structure
- Language: Rust
- Homepage:
- Size: 28.5 MB
- Stars: 18
- Watchers: 4
- Forks: 2
- Open Issues: 5
-
Metadata Files:
- Readme: README.md
- License: LICENSE.md
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README
# Folddisco
Folddisco is a bioinformatics tool for indexing and searching discontinuous motifs in protein structures.
It is designed to handle large-scale protein databases with unmatched speed and efficiency,
enabling the detection of structural motifs across thousands of proteomes or millions of structures.
## Features
- Reduced index size, which enables large databases like AlphaFold to fit on a single disk
- Side-chain orientation-capturing feature and frequency-based scoring for higher precision
- Multi-threaded processing for fast indexing and querying
## Installation
### Default Installation
```bash
cargo install --features foldcomp --path .
```
### Build from Source
```bash
cargo build --release --features foldcomp
# Binary is located at target/release/folddisco
```
## Commands
### Indexing
#### Examples
```bash
# Default indexing for a small dataset
# h_sapiens directory or foldcomp database is indexed with default parameters
folddisco index -p h_sapiens -i index/h_sapiens -t 12
# Indexing big protein dataset
folddisco index -p swissprot -i index/swissprot -t 64 -m big -v
# Indexing with custom hash type and parameters
folddisco index -p h_sapiens -i index/h_sapiens -t 12 --type default -d 16 -a 4 # Default
folddisco index -p h_sapiens -i index/h_sapiens -t 12 --type pdb -d 8 -a 3 # PDB
```
#### Default Usage
```bash
folddisco index -p -i -t
```
#### For Large Databases
```bash
folddisco index -p -i -t -m big
```
- **Mode `big`:** Generates an 8GB fixed-size offset file suitable for datasets with more than 65,536 structures.
#### Custom Binning and Features
```bash
folddisco index -p -i -t -d -a -y
```
#### Example: Indexing the Human Proteome
```bash
folddisco index -p h_sapiens -i index/h_sapiens_folddisco -t 12
```
#### Pre-built Indices
Download pre-built index files:
- [Human proteome](https://foldcomp.steineggerlab.workers.dev/h_sapiens_folddisco.tar.gz)
- [E. coli proteome](https://foldcomp.steineggerlab.workers.dev/e_coli_folddisco.tar.gz)
### Querying
> ## **NOTE:** `-r` flag has been removed. Now, residue matching and RMSD calculation are enabled by default. If you want to skip residue matching and RMSD calculation, use `--skip-match`.
#### Examples
```bash
# Search with default settings. This will print out matching motifs with sorting by RMSD.
folddisco query -p query/4CHA.pdb -q B57,B102,C195 -i index/h_sapiens_folddisco -t 6
folddisco query -p query/1G2F.pdb -q F207,F212,F225,F229 -i index/h_sapiens_folddisco -d 0.5 -a 5 -t 6
folddisco query -p query/1LAP.pdb -q 250,255,273,332,334 -i index/h_sapiens_folddisco --skip-match -t 6 # Skip residue matching
# Query file given as separate text file
folddisco query -q query/zinc_finger.txt -i index/h_sapiens_folddisco -t 6 -d 0.5 -a 5
# Querying a whole structure
folddisco query -i index/h_sapiens_folddisco -p query/1G2F.pdb -t 6 --skip-match
# For a long query, low `--sampling-ratio` can be used to speed up the search
folddisco query -i index/h_sapiens_folddisco -p query/1G2F.pdb -t 6 --skip-match --sampling-ratio 0.3
# Using a query file with distance and angle thresholds
folddisco query -i index/h_sapiens_folddisco -q query/knottin.txt -d 0.5 -a 5 --skip-match -t 6
# Query with amino-acid substitutions and range.
# Alternative amino acids can be given after colon.
# X: substitute to any amino acid, p: positive-charged, n: negative-charged, h: hydrophilic, b: hydrophobic, a: aromatic
# Here's enolase query with 3 substitutions; Allow His at 164, Asp & Asn at 247, and His at 297.
folddisco query -p query/2MNR.pdb -q 164:H,195,221,247:ND,297:H -i index/e_coli_folddisco -d 0.5 -a 5 --top 10 --header --per-structure
# Range can be given with dash. This will query first 10 residues and 11th residue with subsitution to any amino acid.
folddisco query -p query/4CHA.pdb -q 1-10,11:X -i index/h_sapiens_folddisco -t 6 --serial-index
# Advanced query with filtering and sorting
## Based on connected node and rmsd
folddisco query -q query/zinc_finger.txt -i index/h_sapiens_folddisco -t 6 --connected-node 0.75 --rmsd 1.0
## Coverage based filtering & top N filtering without residue matching
folddisco query -q query/zinc_finger.txt -i index/h_sapiens_folddisco -t 6 --covered-node 3 --top 1000 --per-structure --skip-match
# Print top 100 structures with sorting by score
folddisco query -p query/4CHA.pdb -q B57,B102,C195 -i index/h_sapiens_folddisco -t 6 --top 100 --per-structure --sort-by-score
folddisco query -q query/zinc_finger.txt -i index/h_sapiens_folddisco -t 6 --covered-node 4 --top 100 --sort-by-score --per-structure --skip-match
```
#### Default Usage
```bash
folddisco query -i -p -q --skip-match -t
```
- `--skip-match`: Skips residue matching and RMSD calculation.
- `-v`: Verbose output.
#### Whole Structure as Query
```bash
folddisco query -i -p --skip-match -t
```
#### Using a Query File
```bash
folddisco query -i -q --skip-match -t
```
#### Distance and Angle Thresholds
```bash
folddisco query -i -p -q -d -a --skip-match -t
```
## Output
### Match Result
Default output which prints out one matching motif per line
```
id node_count avg_idf rmsd matching_residues query_residues
AF-P00957-F1-model_v4.pdb 3 48.7694 0.2861 _,A666,A564,A568 F207,F212,F225,F229
AF-P0A6K3-F1-model_v4.pdb 3 58.2650 0.4315 A91,_,A133,A137 F207,F212,F225,F229
AF-P26649-F1-model_v4.pdb 2 36.0934 0.2204 A53,_,A22,_ F207,F212,F225,F229
AF-P05020-F1-model_v4.pdb 2 50.9269 0.3112 _,_,A17,A19 F207,F212,F225,F229
AF-P55798-F1-model_v4.pdb 2 62.1218 0.3725 _,_,A132,A14 F207,F212,F225,F229
```
- `id`: Identifier of the protein structure
- `node_count`: Number of nodes in the match
- `idf_score`: Inverse document frequency score of matched structure
- `rmsd`: Root mean square deviation
- `matching_residues`: Residue indices in the match (comma-separated, _ for no match)
- `query_residues`: Residue indices in the query (comma-separated)
### Structure Result
Output with one structure per line (`--per-structure`)
```
id idf_score total_match_count node_count edge_count max_node_cov min_rmsd nres plddt matching_residues query_residues
AF-P55798-F1-model_v4.pdb 62.1218 4 3 4 2 0.3725 218 95.4576 ,,A132,A14:0.3725;,A39,A18,:0.6083 F207,F212,F225,F229
AF-P0A6K3-F1-model_v4.pdb 58.2650 4 3 4 3 0.4315 169 97.1329 A91,_,A133,A137:0.4315 F207,F212,F225,F229
AF-P05020-F1-model_v4.pdb 50.9269 4 3 4 3 0.4391 348 97.0974 ,,A17,A19:0.3112;_,A222,A178,A203:0.4391 F207,F212,F225,F229
AF-P00957-F1-model_v4.pdb 48.7694 4 3 4 3 0.2861 876 90.7232 _,A666,A564,A568:0.2861 F207,F212,F225,F229
AF-P26649-F1-model_v4.pdb 36.0934 2 2 2 2 0.2204 66 75.4210 A53,,A22,:0.2204 F207,F212,F225,F229
```
- `id`: Identifier of the protein structure
- `idf_score`: Inverse document frequency score with length penalty; Higher score indicates more matches within smaller structures
- `total_match_count`: Total number of matches
- `node_count`: Number of nodes in the structure
- `edge_count`: Number of edges in the structure
- `max_node_cov`: Maximum node coverage
- `min_rmsd`: Minimum root mean square deviation
- `nres`: Number of residues
- `plddt`: Predicted local distance difference test score
- `matching_residues`: Residue indices in the match (comma-separated, _ for no match, semicolon-separated for multiple matches with RMSD)
- `query_residues`: Residue indices in the query (comma-separated)
### Display Options
- `--per-structure`: Outputs results per structure.
- `--per-match`: Outputs results per match.
- `--sort-by-score`: Sorts by score.
- `--sort-by-rmsd`: Sorts by RMSD.
- `--top `: Outputs top N results.
- `--header`: Outputs header for the result.
## Example Index List
- **Human proteome:** `index/h_sapiens_folddisco` (23K structures, [Download](https://foldcomp.steineggerlab.workers.dev/h_sapiens_folddisco.tar.gz))
- **E. coli proteome:** `index/e_coli_folddisco` (4K structures, [Download](https://foldcomp.steineggerlab.workers.dev/e_coli_folddisco.tar.gz))
## Example Query List
- `query/`
- `1G2F.pdb`: Zinc finger protein
- `4CHA.pdb`: Serine protease
- `1LAP.pdb`: Aminopeptidase
- `zinc_finger.txt`: 1G2F.pdb F207,F212,F225,F229
- `serine_protease.txt`: 4CHA.pdb B57,B102,C195
- `aminopeptidase.txt`: 1LAP.pdb 250,255,273,332,334
- `knottin.txt`: 2N6N.pdb 3,10,15,16,21,23,28,30
- `enolase.txt`: 2MNR.pdb 164:H,195,221,247:ND,297:H
## Contributions
