foldseek

Software suite for searching and clustering protein structures. Foldseek is a collaboration between the Söding and Steinegger Lab.

Version release

Alpha release: July 24, 2021

Installation

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).

# install from bioconda
conda install -c conda-forge -c bioconda foldseek 
# pull docker container
docker pull steineggerlab/foldseek
# 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

Precompiled binaries for other architectures (ARM64, PPC64LE) and very old AMD/Intel CPUs (SSE2 only) are available at https://mmseqs.com/foldseek.

Quick start

easy-search can search single or multiple queries formatted in pdb/mcif 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

Important parameters

-s                       adjusyesornot the sensitivity to speed trade-off (default: 7.5)
--alignment-type         0: 3Di Gotoh-Smith-Waterman, 1: TMalign 
-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

Main Modules

• easy-search fast protein structure search
• easy-cluster cluster protein structures
• createdb create a database from protein structures (PDB,mmCIF, mmJSON)

Compile from source

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 and foldseek will not be able to run multi-threaded. Adjust the cmake call above to:

CC="$(brew --prefix)/bin/gcc-10" CXX="$(brew --prefix)/bin/g++-10" cmake -DCMAKE_BUILD_TYPE=RELEASE -DCMAKE_INSTALL_PREFIX=. ..

Hardware requirements

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.