Command: foldseek

Usage:
foldseek  chain-spec  [ database  structure-database ] [ showTable  true | false ] [ trim  true | false | chains,sequence,ligands ] [ alignmentCutoffDistance  dist ] [ saveDirectory  results-folder ] [ wait  true | false ]

The foldseek command performs a fast 3D structure search of the PDB or AlphaFold Database for structures similar to a protein chain already open in ChimeraX. The Foldseek (Similar Structures) tool provides a graphical interface to running this command. See also: similarstructures, sequence search, blastprotein

The Foldseek method finds similar 3D structures (regardless of sequence similarity) using extremely fast approaches that were developed for sequence searches. It does so by describing the 3D interactions along a chain of amino acids as a linear sequence of characters, as described in:

Fast and accurate protein structure search with Foldseek. van Kempen M, Kim SS, Tumescheit C, Mirdita M, Lee J, Gilchrist CLM, Söding J, Steinegger M. Nat Biotechnol. 2024 Feb;42(2):243-246.

The search uses the Foldseek Search Service provided by the Söding and Steinegger groups, with maximum number of hits 1000.

The choices of database to search are derived from the Protein Data Bank (PDB) or the AlphaFold Database (AFDB) version 4:

• pdb100 (default) – a redundancy-filtered version of the PDB created with Foldseek (one chain per cluster with 100% sequence identity and ≥95% sequence overlap, reducing ~1 million chains to 340,000)
• afdb50 – UniProt50 subset of Alphafold DB (AFDB)
• afdb-swissprot – SwissProt subset of AFDB (details...)
• afdb-proteome – proteomes subset of AFDB (details...)

The showTable option (default true) indicates whether to show the results in the Similar Structures tool, which facilitates exploring large sets of protein structures by efficiently showing them in 3D as backbone traces and in 2D as sequence alignment schematics or scatter plots based on conformation. Even if the table is not shown, the results can still be analyzed in those ways by referring to them by name (fs1 or fs2) in similarstructures commands. The Log reports the name assigned to the results when the search is run.

The trim and alignmentCutoffDistance options do not act immediately. Instead, they specify how to process the hit structures if later opened from the Similar Structures tool or with the command similarstructures open. The structures are fetched from the respective database (Protein Data Bank or AlphaFold Database) and processed as follows:

• The trim option indicates deleting all of the following (if true, default), or none of them (if false), or a comma-separated list of:
  • chains – for PDB entries, chains other than the hit chain
  • sequence – N- and C-terminal segments of the hit chain that were not included in the sequence alignment returned by the search method
  • ligands – ligands, solvent, and ions > 3 Å from the hit chain
  The trim default is the current setting in the Similar Structures options, otherwise (if the tool is not open) true.
  
  
• The hit chain is superimposed onto the query chain by least-squares fitting the α-carbons of the paired residues and iteratively pruning far-apart pairs as described for the align command. The alignmentCutoffDistance d is the alignment pruning distance so that only α-carbon pairs within the specified distance are used in the final fit (default as per the Similar Structures options, otherwise 2.0 Å)

Search results are saved in a similar structures file (suffix .sms, a JSON file format specific to ChimeraX) with filename based on the query name and the database searched. The file will be listed in the File History for easy access, and simply opening it loads the set of results into the Similar Structures interface. The saveDirectory option allows specifying the save location, either directly or as the word browse to specify it interactively in a file browser window (default location ~/Downloads/ChimeraX/Foldseek/).

By default (wait false), the search is run in the background so that ChimeraX can be used for other tasks at the same time. Specifying wait true makes ChimeraX wait until the search completes before executing any subsequent commands; this may be necessary in command scripts that process the output.