Publication detail

FireProt 2.0: Web-based Platform for the Fully-Automated Design of Thermostable Proteins

MUSIL, M. JEŽÍK, A. HORÁČKOVÁ, J. BORKO, S. KABOUREK, P. DAMBORSKÝ, J. BEDNÁŘ, D.

Original Title

FireProt 2.0: Web-based Platform for the Fully-Automated Design of Thermostable Proteins

Type

journal article in Scopus

Language

English

Original Abstract

Thermostable proteins find their use in numerous biomedical and biotechnological applications. However, the computational design of stable proteins often results in single-point mutations with a limited effect on protein stability. However, the construction of stable multiple-point mutants can prove difficult due to the possibility of antagonistic effects between individual mutations. FireProt protocol enables the automated computational design of highly stable multiple-point mutants. FireProt 2.0 builds on top of the previously published FireProt web, retaining the original functionality and expanding it with several new stabilization strategies. FireProt 2.0 integrates the AlphaFold database and the homology modelling for structure prediction, enabling calculations starting from a sequence. Multiple-point designs are constructed using the Bron-Kerbosch algorithm minimizing the antagonistic effect between the individual mutations. Users can newly limit the FireProt calculation to a set of user-defined mutations, run a saturation mutagenesis of the whole protein, or select rigidifying mutations based on B-factors. Evolution-based back-to-consensus strategy is complemented by ancestral sequence reconstruction. FireProt 2.0 is significantly faster and a reworked graphical user interface broadens the tool's availability even to users with older hardware. FireProt 2.0 is freely available at http://loschmidt.chemi.muni.cz/fireprotweb.

Keywords

ancestral, back-to-consensus, B-factor, epistasis, evolution, force-field, multiple-point mutant, protein engineering, saturation mutagenesis, thermostability

Authors

MUSIL, M.; JEŽÍK, A.; HORÁČKOVÁ, J.; BORKO, S.; KABOUREK, P.; DAMBORSKÝ, J.; BEDNÁŘ, D.

Released

2. 11. 2023

ISBN

1467-5463

Periodical

BRIEFINGS IN BIOINFORMATICS

Year of study

25

Number

1

State

United Kingdom of Great Britain and Northern Ireland

Pages from

1

Pages to

10

Pages count

17

URL

https://www.fit.vut.cz/research/publication/13097/

BibTex

@article{BUT185670,
  author="Miloš {Musil} and Andrej {Ježík} and Jana {Horáčková} and Simeon {Borko} and Petr {Kabourek} and Jiří {Damborský} and David {Bednář}",
  title="FireProt 2.0: Web-based Platform for the Fully-Automated Design of Thermostable Proteins",
  journal="BRIEFINGS IN BIOINFORMATICS",
  year="2023",
  volume="25",
  number="1",
  pages="1--10",
  doi="10.1093/bib/bbad425",
  issn="1467-5463",
  url="https://www.fit.vut.cz/research/publication/13097/"
}

Documents

FireProt2.pdf
Supplementary_table_S2.xlsx
Supplementary_table_S1.xlsx
Supplementary_table_S3.xlsx