Using AlphaFold to predict the impact of single mutations on protein stability and function

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 AlphaFoldtriggered 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. © 2023 Pak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Авторы
Pak M.A. , Markhieva K.A. , Novikova M.S. , Petrov D.S. , Vorobyev I.S. , Maksimova E.S. , Kondrashov F.A. , Ivankov D.N.
Журнал
Издательство
Public Library of Science
Номер выпуска
3 March
Язык
Английский
Статус
Опубликовано
Номер
e0282689
Том
18
Год
2023
Организации
  • 1 Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russian Federation
  • 2 Peoples' Friendship University of Russia (RUDN University), Moscow, Russian Federation
  • 3 Armand Hammer United World College of the American West, Montezuma, NM, United States
  • 4 Specialized Educational and Scientific Center of UrFU (SUNC UrFU), Ekaterinburg, Russian Federation
  • 5 Institute of Science and Technology Austria, Maria Gugging, Austria
  • 6 Evolutionary and Synthetic Biology Unit, Okinawa Institute of Science and Technology Graduate University, Onna, Okinawa, Japan
Ключевые слова
Amino Acid Sequence; Mutation; Protein Folding; Protein Stability; Proteins; protein; article; fluorescence; prediction; protein folding; protein function; protein stability; amino acid sequence; chemistry; mutation; protein folding; protein stability
Цитировать
Поделиться

Другие записи