PDBe-SIFTS: An open-source tool for Structure Integration with Function, Taxonomy, and Sequences, featuring improved alignment, scoring scheme, and accelerated search.
- 1Protein Data Bank in Europe, European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridgeshire, UK.
- 2Protein Function Content, European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridgeshire, UK.
- 3Protein Function Development, European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridgeshire, UK.
Abstract
Structure integration with function, taxonomy and sequences (SIFTS) provides residue-level mappings between UniProt Knowledgebase sequences and Protein Data Bank structures and has historically been generated through internal Protein Data Bank in Europe (PDBe) pipelines. Here, PDBe-SIFTS is presented as a fully open-source, locally deployable implementation of this mapping framework. The pipeline combines fast, scalable sequence search using MMseqs2, an improved bounded scoring scheme for ranking candidate mappings, and residue-level mapping refinement based on backbone connectivity. PDBe-SIFTS is distributed as a Python package with command-line tools for (1) building a sequence search database, (2) identifying the best sequence-structure match, (3) one-to-one mapping at the residue level, and (4) generating SIFTS annotations in PDBx/mmCIF format. Benchmarking on the complete Protein Data Bank archive showed that MMseqs2 reduced archive-scale UniProtKB searches from hours with BLASTP to minutes, approximately 22-36 times faster, while curated mappings were recovered at top rank in 93.1% of cases. The remaining discrepancies mainly involved biologically ambiguous cases such as highly conserved proteins, chimeric constructs, or closely related orthologs. These results show that PDBe-SIFTS enables fast mapping, improving structural coherence in residue-level alignments while delivering the most up-to-date and accurate mappings, comparable to expert curation. Tool: https://github.com/PDBeurope/SIFTS. Quick start notebook with example: https://github.com/PDBeurope/SIFTS/tree/master/notebooks.
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BibTeX
@article{bellaiche2026pdbesifts,
title = {{PDBe-SIFTS: An open-source tool for Structure Integration with Function, Taxonomy, and Sequences, featuring improved alignment, scoring scheme, and accelerated search.}},
author = {Adam Bellaiche and Preeti Choudhary and Sreenath Nair and Deborah Harrus and Conny Wing-Heng Yu and Syed Ahsan Tanweer and Genevieve Laura Evans and Stephanie W Lo and Maria J Martin and Jennifer R Fleming and Sameer Velankar},
journal = {Protein science : a publication of the Protein Society},
year = {2026},
month = oct,
doi = {10.1002/pro.70819},
url = {https://europepmc.org/article/MED/42885203},
note = {CC BY},
}
RIS
TY - JOUR
TI - PDBe-SIFTS: An open-source tool for Structure Integration with Function, Taxonomy, and Sequences, featuring improved alignment, scoring scheme, and accelerated search.
AU - Adam Bellaiche
AU - Preeti Choudhary
AU - Sreenath Nair
AU - Deborah Harrus
AU - Conny Wing-Heng Yu
AU - Syed Ahsan Tanweer
AU - Genevieve Laura Evans
AU - Stephanie W Lo
AU - Maria J Martin
AU - Jennifer R Fleming
AU - Sameer Velankar
PY - 2026
DA - 2026/10/30
JO - Protein science : a publication of the Protein Society
DO - 10.1002/pro.70819
UR - https://europepmc.org/article/MED/42885203
AB - Structure integration with function, taxonomy and sequences (SIFTS) provides residue-level mappings between UniProt Knowledgebase sequences and Protein Data Bank structures and has historically been generated through internal Protein Data Bank in Europe (PDBe) pipelines. Here, PDBe-SIFTS is presented as a fully open-source, locally deployable implementation of this mapping framework. The pipeline combines fast, scalable sequence search using MMseqs2, an improved bounded scoring scheme for ranking candidate mappings, and residue-level mapping refinement based on backbone connectivity. PDBe-SIFTS is distributed as a Python package with command-line tools for (1) building a sequence search database, (2) identifying the best sequence-structure match, (3) one-to-one mapping at the residue level, and (4) generating SIFTS annotations in PDBx/mmCIF format. Benchmarking on the complete Protein Data Bank archive showed that MMseqs2 reduced archive-scale UniProtKB searches from hours with BLASTP to minutes, approximately 22-36 times faster, while curated mappings were recovered at top rank in 93.1% of cases. The remaining discrepancies mainly involved biologically ambiguous cases such as highly conserved proteins, chimeric constructs, or closely related orthologs. These results show that PDBe-SIFTS enables fast mapping, improving structural coherence in residue-level alignments while delivering the most up-to-date and accurate mappings, comparable to expert curation. Tool: https://github.com/PDBeurope/SIFTS. Quick start notebook with example: https://github.com/PDBeurope/SIFTS/tree/master/notebooks.
SN - 0961-8368
SN - 1469-896X
ER -