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Bellaiche, A.

Publications and source records attributed to Bellaiche, A..

2 recordsLinked to original sources
bioRxiv2026

PDBe-SIFTS: an open-source tool for Structure Integration with Function, Taxonomy, and Sequences, featuring improved alignment, scoring scheme, and accelerated search

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 Broader audience statementMatching protein sequences to their three-dimensional structures, and mapping annotations across both, is essential for understanding protein function, interactions, and molecular mechanisms. This integrated view enables richer interpretation of biological data and underpins advances in drug discovery, disease research, and protein engineering. PDBe-SIFTS provides an open and functional framework for structure-sequence mapping, allowing researchers and databases to run, inspect, and extend these mappings locally, while benefiting from faster searches, transparent scoring, and structurally informed residue-level alignments. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/721839v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@5e6ea6org.highwire.dtl.DTLVardef@1b2754dorg.highwire.dtl.DTLVardef@1334f9forg.highwire.dtl.DTLVardef@1b083a1_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗
bioRxiv2026

Impact of the N-glycosylation on full-length IgG2 and IgG4 antibodies: a comparative study using molecular dynamics simulations.

Monoclonal antibodies are among the most important biomolecules in the pharmaceutic field. They could undergo several post-translational modifications, most notably N-glycosylation, yet the effect of these glycans remains poorly understood at the atomistic level, and the few existing studies focus on the prevalent immunoglobulin G1. We compared N-glycosylation in two structurally divergent monoclonal antibodies, Mab231, a murine IgG2a, and pembrolizumab, a human IgG4, which differ in species, sequence, architecture, and in the location and composition of their glycans. Using molecular dynamics simulations, we studied both antibodies with and without their glycans. In both, the glycan interactions extend beyond the Fc to reach Fab residues, more so for the more mobile Fc glycan and differently in the two antibodies. Allosteric network calculations reveal a potential impact of the glycan that can affect the Fab framework regions, which could in turn affect antigen binding. The glycans do not drastically alter the conformational landscape, and neither the inter-domain correlated motions nor the orientation of the Fab arms relative to the Fc can be resolved as glycan effects at three replicates per system. We also find that the effect of the Fc glycans on CH2 opening depends on the geometric criterion used, which underscores the need to consider full-length structures and the diversity of IgG scaffolds in glyco-engineering.

bioinformatics↗