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Cited by 9Protein Structure and DynamicsMachine Learning in BioinformaticsEnzyme Structure and Function

Outer membrane β‐barrel structure prediction through the lens of AlphaFold2

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Topitsch, Annika, Schwede, Torsten, Pereira, Joana·2024·Proteins: Structure, Function, and Bioinformatics
DOI 10.1002/prot.26552

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Abstract

Most proteins found in the outer membrane of gram-negative bacteria share a common domain: the transmembrane β-barrel. These outer membrane β-barrels (OMBBs) occur in multiple sizes and different families with a wide range of functions evolved independently by amplification from a pool of homologous ancestral ββ-hairpins. This is part of the reason why predicting their three-dimensional (3D) structure, especially by homology modeling, is a major challenge. Recently, DeepMind's AlphaFold v2 (AF2) became the first structure prediction method to reach close-to-experimental atomic accuracy in CASP even for difficult targets. However, membrane proteins, especially OMBBs, were not abundant during their training, raising the question of how accurate the predictions are for these families. In this study, we assessed the performance of AF2 in the prediction of OMBBs and OMBB-like folds of various topologies using an in-house-developed tool for the analysis of OMBB 3D structures, and barrOs. In agreement with previous studies on other membrane protein classes, our results indicate that AF2 predicts transmembrane β-barrel structures at high accuracy independently of the use of templates, even for novel topologies absent from the training set. These results provide confidence on the models generated by AF2 and open the door to the structural elucidation of novel transmembrane β-barrel topologies identified in high-throughput OMBB annotation studies or designed de novo.

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Cited by

Sorted by citations

Authors
Topitsch, A., Schwede, T., & Pereira, J.
Affiliations
  • University of Basel (CH)
  • SIB Swiss Institute of Bioinformatics (CH)
Corresponding author
  • Schwede, Torsten
  • Pereira, Joana
ORCID
Venue
Proteins: Structure, Function, and Bioinformatics
Publisher
Wiley
Published
2023-07-19
Volume
92
Issue
1
Pages
3-14
ISSN
  • 0887-3585 (ISSN-L)
  • 1097-0134
DOI
10.1002/prot.26552
OpenAlex
W4384663444
Cited by
9
References
4
Citations by year
2026: 2 · 2025: 5 · 2024: 2
FWCI
0.80
Type
journal article
Language
en
Open access
Licence
Locations
  • Proteins Structure Function and Bioinformatics (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • edoc (University of Basel) (acceptedVersion)
  • FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
  • edoc (University of Basel)
Funders
  • Swiss Institute of Bioinformatics
  • Universität Basel
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords
transmembrane beta-barrel, AlphaFold2, membrane protein structure prediction, Gram-negative bacterial outer membrane, homology modeling, Barros
MeSH terms
Bacterial Outer Membrane Proteins, Furylfuramide, Humans, Membrane Proteins

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