Foldseek enables fast and sensitive comparisons of large structure sets. It reaches sensitivities similar to state-of-the-art structural aligners while being at least 20,000 times faster.
Search your protein structures against the AlphaFoldDB and PDB in seconds using our Foldseek webserver:
foldseek can be used by compiling from source (see below) or downloading a statically compiled version. It requires a 64-bit system. We recommend using a system with at least the SSE4.1 instruction set (check by executing cat /proc/cpuinfo | grep sse4_1 on Linux).
# static Linux AVX2 build
wget https://mmseqs.com/foldseek/foldseek-linux-avx2.tar.gz; tar xvzf foldseek-linux-avx2.tar.gz; export PATH=$(pwd)/foldseek/bin/:$PATH
# static Linux SSE4.1 build
wget https://mmseqs.com/foldseek/foldseek-linux-sse41.tar.gz; tar xvzf foldseek-linux-sse41.tar.gz; export PATH=$(pwd)/foldseek/bin/:$PATH
# static macOS build (universal binary with SSE4.1/AVX2/M1 NEON)
wget https://mmseqs.com/foldseek/foldseek-osx-universal.tar.gz; tar xvzf foldseek-osx-universal.tar.gz; export PATH=$(pwd)/foldseek/bin/:$PATH
# conda installer
conda install -c conda-forge -c bioconda foldseek
Precompiled binaries for other architectures (ARM64, PPC64LE) and very old AMD/Intel CPUs (SSE2 only) are available at https://mmseqs.com/foldseek.
easy-search can search single or multiple queries formatted in PDB/mmCIF format (flat or .gz) against a target database (example/) of protein structures. It outputs a tab-separated file of the alignments (.m8) the fields are query,target,fident,alnlen,mismatch,gapopen,qstart,qend,tstart,tend,evalue,bits.
foldseek easy-search example/d1asha_ example/ aln.m8 tmpFolder
The output can be customized with the --format-output option e.g. --format-output "query,target,qaln,taln" returns the query and target accession and the pairwise alignments in tab separated format.
You can choose many different output columns.
The target database can be pre-processed by createdb. This make sense if searched multiple times.
foldseek createdb example/ targetDB
foldseek easy-search example/d1asha_ targetDB aln.m8 tmpFolder
-s adjust the sensitivity to speed trade-off.
lower is faster, higher more sensitive (fast: 7.5, highest sensitivity (default): 9.5)
--max-seqs adjust the amount of prefilter that are handed to the alignment.
Increasing it can lead to more hits (default: 300)
--alignment-type 0: 3Di Gotoh-Smith-Waterman (local, not recommended),
1: TMalign (global),
2: 3Di+AA Gotoh-Smith-Waterman (local, default)
-c list matches above this fraction of aligned (covered) residues (see --cov-mode) (default: 0.0)
--cov-mode 0: coverage of query and target, 1: coverage of target, 2: coverage of query
Setup the PDB or AlphaFoldDB using the databases module.
# pdb
foldseek databases PDB pdb tmp
# alphafold db
foldseek databases Alphafold/Proteome afdb tmp
We currently support the following databases:
Name Type Taxonomy Url
- Alphafold/Proteome Aminoacid yes https://alphafold.ebi.ac.uk/
- Alphafold/Swiss-Prot Aminoacid yes https://alphafold.ebi.ac.uk/
- PDB Aminoacid yes https://www.rcsb.org
easy-searchfast protein structure searchcreatedbcreate a database from protein structures (PDB,mmCIF, mmJSON)databasesdownload pre-assembled databases
Foldseek supports to realign hits using TMalign as well as rescoring alignments using TMscore.
In case of the alignment type (--alignment-type 1) tmalign we sort the results by the TMscore normalized by query length. We write the TMscore into the e-value(=TMscore) as well as into the score(=TMscore*100) field.
foldseek easy-search example/d1asha_ example/ aln tmp --alignment-type 1
It is possible to compute TMscores for the kind of alignment output (e.g. 3Di/AA) using the following commands:
foldseek createdb example/ targetDB
foldseek createdb example/ queryDB
foldseek search queryDB targetDB aln tmpFolder -a
foldseek aln2tmscore queryDB targetDB aln aln_tmscore
foldseek createtsv queryDB targetDB aln_tmscore aln_tmscore.tsv
In the output is the query and target identifier, TMscore, translation(3) and rotation vector=(3x3) (query,target,TMscore,t[0-2],u[0-2][0-2])
Foldseek can locally generate search results resembling what is displayed on the
search.foldseek.com webserver by specifying the HTML
format mode (--format-mode 3).
foldseek easy-search example/d1asha_ example/ result.html tmp --format-mode 3
Compiling foldseek from source has the advantage of system-specific optimizations, which should improve its performance. To compile it git, g++ (4.9 or higher) and cmake (3.0 or higher) are required. Afterwards, the foldseek binary will be located in the build/bin directory.
git clone https://github.com/steineggerlab/foldseek.git
cd foldseek
mkdir build
cd build
cmake -DCMAKE_BUILD_TYPE=RELEASE -DCMAKE_INSTALL_PREFIX=. ..
make -j
make install
export PATH=$(pwd)/foldseek/bin/:$PATH
❗ If you want to compile foldseek on macOS, please install and use gcc from Homebrew. The default macOS clang compiler does not support OpenMP (by default) and foldseek will not be able to run multi-threaded. Adjust the cmake call above to:
CC="$(brew --prefix)/bin/gcc-11" CXX="$(brew --prefix)/bin/g++-11" cmake -DCMAKE_BUILD_TYPE=RELEASE -DCMAKE_INSTALL_PREFIX=. ..
foldseek will scale its memory consumption based on the available main memory of the machine. foldseek needs a 64-bit CPU with at least the SSE2 instruction set to run.
