Knot or not? Identifying unknotted proteins in knotted families with sequence-based Machine Learning model

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F24%3A00136613" target="_blank" >RIV/00216224:14740/24:00136613 - isvavai.cz</a>

Result on the web

<a href="https://onlinelibrary.wiley.com/doi/10.1002/pro.4998" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1002/pro.4998</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/pro.4998" target="_blank" >10.1002/pro.4998</a>

Result language

angličtina

Original language name

Knot or not? Identifying unknotted proteins in knotted families with sequence-based Machine Learning model

Original language description

Knotted proteins, although scarce, are crucial structural components of certain protein families, and their roles continue to be a topic of intense research. Capitalizing on the vast collection of protein structure predictions offered by AlphaFold (AF), this study computationally examines the entire UniProt database to create a robust dataset of knotted and unknotted proteins. Utilizing this dataset, we develop a machine learning (ML) model capable of accurately predicting the presence of knots in protein structures solely from their amino acid sequences. We tested the model's capabilities on 100 proteins whose structures had not yet been predicted by AF and found agreement with our local prediction in 92% cases. From the point of view of structural biology, we found that all potentially knotted proteins predicted by AF can be classified only into 17 families. This allows us to discover the presence of unknotted proteins in families with a highly conserved knot. We found only three new protein families: UCH, DUF4253, and DUF2254, that contain both knotted and unknotted proteins, and demonstrate that deletions within the knot core could potentially account for the observed unknotted (trivial) topology. Finally, we have shown that in the majority of knotted families (11 out of 15), the knotted topology is strictly conserved in functional proteins with very low sequence similarity. We have conclusively demonstrated that proteins AF predicts as unknotted are structurally accurate in their unknotted configurations. However, these proteins often represent nonfunctional fragments, lacking significant portions of the knot core (amino acid sequence).

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Protein Science

ISSN

0961-8368

e-ISSN

—

Volume of the periodical

33

Issue of the periodical within the volume

7

Country of publishing house

US - UNITED STATES

Number of pages

21

Pages from-to

1-21

UT code for WoS article

001251031800001

EID of the result in the Scopus database

2-s2.0-85196320912