---
_id: '12758'
abstract:
- lang: eng
  text: AlphaFold changed the field of structural biology by achieving three-dimensional
    (3D) structure prediction from protein sequence at experimental quality. The astounding
    success even led to claims that the protein folding problem is “solved”. However,
    protein folding problem is more than just structure prediction from sequence.
    Presently, it is unknown if the AlphaFold-triggered revolution could help to solve
    other problems related to protein folding. Here we assay the ability of AlphaFold
    to predict the impact of single mutations on protein stability (ΔΔG) and function.
    To study the question we extracted the pLDDT and <pLDDT> metrics from AlphaFold
    predictions before and after single mutation in a protein and correlated the predicted
    change with the experimentally known ΔΔG values. Additionally, we correlated the
    same AlphaFold pLDDT metrics with the impact of a single mutation on structure
    using a large scale dataset of single mutations in GFP with the experimentally
    assayed levels of fluorescence. We found a very weak or no correlation between
    AlphaFold output metrics and change of protein stability or fluorescence. Our
    results imply that AlphaFold may not be immediately applied to other problems
    or applications in protein folding.
acknowledgement: The authors acknowledge the use of Zhores supercomputer [28] for
  obtaining the results presented in this paper.The authors thank Zimin Foundation
  and Petrovax for support of the presented study at the School of Molecular and Theoretical
  Biology 2021.
article_number: e0282689
article_processing_charge: No
article_type: original
author:
- first_name: Marina A.
  full_name: Pak, Marina A.
  last_name: Pak
- first_name: Karina A.
  full_name: Markhieva, Karina A.
  last_name: Markhieva
- first_name: Mariia S.
  full_name: Novikova, Mariia S.
  last_name: Novikova
- first_name: Dmitry S.
  full_name: Petrov, Dmitry S.
  last_name: Petrov
- first_name: Ilya S.
  full_name: Vorobyev, Ilya S.
  last_name: Vorobyev
- first_name: Ekaterina
  full_name: Maksimova, Ekaterina
  id: 2FBE0DE4-F248-11E8-B48F-1D18A9856A87
  last_name: Maksimova
- first_name: Fyodor
  full_name: Kondrashov, Fyodor
  id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
  last_name: Kondrashov
  orcid: 0000-0001-8243-4694
- first_name: Dmitry N.
  full_name: Ivankov, Dmitry N.
  last_name: Ivankov
citation:
  ama: Pak MA, Markhieva KA, Novikova MS, et al. Using AlphaFold to predict the impact
    of single mutations on protein stability and function. <i>PLoS ONE</i>. 2023;18(3).
    doi:<a href="https://doi.org/10.1371/journal.pone.0282689">10.1371/journal.pone.0282689</a>
  apa: Pak, M. A., Markhieva, K. A., Novikova, M. S., Petrov, D. S., Vorobyev, I.
    S., Maksimova, E., … Ivankov, D. N. (2023). Using AlphaFold to predict the impact
    of single mutations on protein stability and function. <i>PLoS ONE</i>. Public
    Library of Science. <a href="https://doi.org/10.1371/journal.pone.0282689">https://doi.org/10.1371/journal.pone.0282689</a>
  chicago: Pak, Marina A., Karina A. Markhieva, Mariia S. Novikova, Dmitry S. Petrov,
    Ilya S. Vorobyev, Ekaterina Maksimova, Fyodor Kondrashov, and Dmitry N. Ivankov.
    “Using AlphaFold to Predict the Impact of Single Mutations on Protein Stability
    and Function.” <i>PLoS ONE</i>. Public Library of Science, 2023. <a href="https://doi.org/10.1371/journal.pone.0282689">https://doi.org/10.1371/journal.pone.0282689</a>.
  ieee: M. A. Pak <i>et al.</i>, “Using AlphaFold to predict the impact of single
    mutations on protein stability and function,” <i>PLoS ONE</i>, vol. 18, no. 3.
    Public Library of Science, 2023.
  ista: Pak MA, Markhieva KA, Novikova MS, Petrov DS, Vorobyev IS, Maksimova E, Kondrashov
    F, Ivankov DN. 2023. Using AlphaFold to predict the impact of single mutations
    on protein stability and function. PLoS ONE. 18(3), e0282689.
  mla: Pak, Marina A., et al. “Using AlphaFold to Predict the Impact of Single Mutations
    on Protein Stability and Function.” <i>PLoS ONE</i>, vol. 18, no. 3, e0282689,
    Public Library of Science, 2023, doi:<a href="https://doi.org/10.1371/journal.pone.0282689">10.1371/journal.pone.0282689</a>.
  short: M.A. Pak, K.A. Markhieva, M.S. Novikova, D.S. Petrov, I.S. Vorobyev, E. Maksimova,
    F. Kondrashov, D.N. Ivankov, PLoS ONE 18 (2023).
date_created: 2023-03-26T22:01:07Z
date_published: 2023-03-16T00:00:00Z
date_updated: 2023-08-01T13:47:14Z
day: '16'
ddc:
- '570'
department:
- _id: FyKo
- _id: MaRo
doi: 10.1371/journal.pone.0282689
external_id:
  isi:
  - '000985134400106'
file:
- access_level: open_access
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  creator: dernst
  date_created: 2023-03-27T07:09:08Z
  date_updated: 2023-03-27T07:09:08Z
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  file_name: 2023_PLoSOne_Pak.pdf
  file_size: 856625
  relation: main_file
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file_date_updated: 2023-03-27T07:09:08Z
has_accepted_license: '1'
intvolume: '        18'
isi: 1
issue: '3'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
publication: PLoS ONE
publication_identifier:
  eissn:
  - 1932-6203
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: Using AlphaFold to predict the impact of single mutations on protein stability
  and function
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 18
year: '2023'
...