reseek

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Reseek is a protein structure search and alignment algorithm which improves sensitivity in protein homolog detection compared to state-of-the-art methods including DALI, TM-align and Foldseek with similar speed to Foldseek.

Reseek is based on sequence alignment where each residue in the protein backbone is represented by a letter in a novel “mega-alphabet” of 85,899,345,920 (∼10¹¹) distinct states.

Method sensitivity was measured on the SCOP40 benchmark using superfamily as the truth standard, focusing on the regime with false-positive error rates <10 per query, corresponding to E<10 for an ideal E-value.

Command line

  -search        # Alignment (e.g. DB search, pairwise, all-vs-all)
  -convert       # Convert file formats (e.g. create DB)
  -alignpair     # Pair-wise alignment and superposition

Search against database
    reseek -search STRUCTS -db STRUCTS -output hits.txt
                 # STRUCTS specifies structure(s), see below

Recommended format for large database is .bca, e.g.
    reseek -convert /data/PDB_mirror/ -bca PDB.bca

Align and superpose two structures
    reseek -alignpair 1XYZ.pdb -input2 2ABC.pdb
           -aln FILE     # Sequence alignment (text)
           -output FILE  # Rotated 1XYZ (PDB format)

All-vs-all alignment
    reseek -search STRUCTS -output hits.txt

Output options for -search
   -aln FILE     # Alignments in human-readable format
   -output FILE  # Hits in tabbed text format
   -columns name1+name2+name3...
                 # Output columns, names are
                 #   query   Query label
                 #   target  Target label
                 #   qlo     Start of aligment in query
                 #   qhi     End of aligment in query
                 #   tlo     Start of aligment in target
                 #   thi     End of aligment in target
                 #   ql      Query length
                 #   tl      Target length
                 #   pctid   Percent identity of alignment
                 #   cigar   CIGAR string
                 #   evalue  You can guess this one
                 #   aq      AQ (aln. qual., 0 to 1, >0.5 suggests homology)
                 #   qrow    Aligned query sequence with gaps (local)
                 #   trow    Aligned target sequence with gaps (local)
                 #   qrowg   Aligned query sequence with gaps (global)
                 #   trowg   Aligned target sequence with gaps (global)
                 #   std     query+target+qlo+qhi+ql+tlo+thi+tl+pctid+evalue
                 # default aq+query+target+evalue

Search and alignment options
  -fast, -sensitive or -verysensitive     # Required
  -evalue E      # Max E-value (default 10 unless -verysensitive)
  -omega X       # Omega accelerator (floating-point)
  -minu U        # K-mer accelerator (integer)
  -gapopen X     # Gap-open penalty (floating-point >= 0)
  -gapext X      # Gap-extend penalty (floating-point >= 0)
  -dbsize D      # DB size (nr. chains) for E-value (default actual size)

Convert between file formats
    reseek -convert STRUCTS [one or more output options]
           -cal FILENAME    # .cal format, text with a.a. and C-alpha x,y,z
           -bca FILENAME    # .bca format, binary .cal, recommended for DBs
           -fasta FILENAME  # FASTA format

Create input for Muscle-3D multiple structure alignment:
    reseek -pdb2mega STRUCTS -output structs.mega

STRUCTS argument is one of:
   NAME.cif or NAME.mmcif     # PDBx/mmCIF file
   NAME.pdb                   # Legacy format PDB file
   NAME.cal                   # C-alpha tabbed text format with chain(s)
   NAME.bca                   # Binary C-alpha, recommended for larger DBs
   NAME.files                 # Text file with one STRUCT per line,
                              #   may be filename, directory or .files
   DIRECTORYNAME              # Directory (and its sub-directories) is searched
                              #   for known file types including .pdb, .files etc.

Other options:
   -log FILENAME              # Log file with errors, warnings, time and memory.
   -threads N                 # Number of threads, default number of CPU cores.

Build from source on Linux x86

cd src/; chmod +x build_linux_x86.bash ; ./build_linux_x86.bash

Build from source on OSX x86

cd src/ ; chmod +x build_osx_x86.bash ; ./build_osx_x86.bash

Build from source on Windows

Load reseek.vcxproj into Microsoft Visual Studio and use the Build command.

Static link warning

Don't worry about a warning something like this, it's expected:

warning: Using 'dlopen' in statically linked applications requires
  at runtime the shared libraries from the glibc version used for linking

More documentation

https://drive5.com/reseek

Reference

Edgar, Robert C. (2024) "Sequence alignment using large protein structure alphabets improves sensitivity to remote homologs" https://www.biorxiv.org/content/10.1101/2024.05.24.595840v2

SCOP40 benchmark code and results

https://github.com/rcedgar/reseek_bench