How AlphaFold2 shaped the structural coverage of the human transmembrane proteome

AlphaFold2 (AF2) provides a 3D structure for every known or predicted protein, opening up new prospects for virtually every field in structural biology. However, working with transmembrane protein molecules pose a notorious challenge for scientists, resulting in a limited number of experimentally de...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2023-11, Vol.13 (1), p.20283-11, Article 20283
Main Authors: Jambrich, Márton A., Tusnady, Gabor E., Dobson, Laszlo
Format: Article
Language:English
Subjects:
631/114/2411
631/535/1267
Algorithms
Databases, Factual
Furylfuramide
Homology
Humanities and Social Sciences
Humans
Membrane Proteins
multidisciplinary
Protein families
Proteins
Proteome
Proteomes
Quality control
Science
Science (multidisciplinary)
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:AlphaFold2 (AF2) provides a 3D structure for every known or predicted protein, opening up new prospects for virtually every field in structural biology. However, working with transmembrane protein molecules pose a notorious challenge for scientists, resulting in a limited number of experimentally determined structures. Consequently, algorithms trained on this finite training set also face difficulties. To address this issue, we recently launched the TmAlphaFold database, where predicted AlphaFold2 structures are embedded into the membrane plane and a quality assessment (plausibility of the membrane-embedded structure) is provided for each prediction using geometrical evaluation. In this paper, we analyze how AF2 has improved the structural coverage of membrane proteins compared to earlier years when only experimental structures were available, and high-throughput structure prediction was greatly limited. We also evaluate how AF2 can be used to search for (distant) homologs in highly diverse protein families. By combining quality assessment and homology search, we can pinpoint protein families where AF2 accuracy is still limited, and experimental structure determination would be desirable.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-47204-7