IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-51776-x.html
   My bibliography  Save this article

An end-to-end framework for the prediction of protein structure and fitness from single sequence

Author

Listed:
  • Yinghui Chen

    (Tsinghua University
    Tsinghua University)

  • Yunxin Xu

    (Tsinghua University
    Tsinghua University)

  • Di Liu

    (Tsinghua University
    Tsinghua University)

  • Yaoguang Xing

    (Tsinghua University
    Tsinghua University)

  • Haipeng Gong

    (Tsinghua University
    Tsinghua University)

Abstract

Significant research progress has been made in the field of protein structure and fitness prediction. Particularly, single-sequence-based structure prediction methods like ESMFold and OmegaFold achieve a balance between inference speed and prediction accuracy, showing promise for many downstream prediction tasks. Here, we propose SPIRED, a single-sequence-based structure prediction model that exhibits comparable performance to the state-of-the-art methods but with approximately 5-fold acceleration in inference and at least one order of magnitude reduction in training consumption. By integrating SPIRED with downstream neural networks, we compose an end-to-end framework named SPIRED-Fitness for the rapid prediction of both protein structure and fitness from single sequence with satisfactory accuracy. Moreover, SPIRED-Stab, the derivative of SPIRED-Fitness, achieves state-of-the-art performance in predicting the mutational effects on protein stability.

Suggested Citation

  • Yinghui Chen & Yunxin Xu & Di Liu & Yaoguang Xing & Haipeng Gong, 2024. "An end-to-end framework for the prediction of protein structure and fitness from single sequence," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51776-x
    DOI: 10.1038/s41467-024-51776-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-51776-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-51776-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Yunan Luo & Guangde Jiang & Tianhao Yu & Yang Liu & Lam Vo & Hantian Ding & Yufeng Su & Wesley Wei Qian & Huimin Zhao & Jian Peng, 2021. "ECNet is an evolutionary context-integrated deep learning framework for protein engineering," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    2. Kotaro Tsuboyama & Justas Dauparas & Jonathan Chen & Elodie Laine & Yasser Mohseni Behbahani & Jonathan J. Weinstein & Niall M. Mangan & Sergey Ovchinnikov & Gabriel J. Rocklin, 2023. "Mega-scale experimental analysis of protein folding stability in biology and design," Nature, Nature, vol. 620(7973), pages 434-444, August.
    3. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    4. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    5. Josh Abramson & Jonas Adler & Jack Dunger & Richard Evans & Tim Green & Alexander Pritzel & Olaf Ronneberger & Lindsay Willmore & Andrew J. Ballard & Joshua Bambrick & Sebastian W. Bodenstein & David , 2024. "Accurate structure prediction of biomolecular interactions with AlphaFold 3," Nature, Nature, vol. 630(8016), pages 493-500, June.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Pantelis Livanos & Choy Kriechbaum & Sophia Remers & Arvid Herrmann & Sabine Müller, 2025. "Kinesin-12 POK2 polarization is a prerequisite for a fully functional division site and aids cell plate positioning," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    2. Justin Riper & Arleth O. Martinez-Claros & Lie Wang & Hannah E. Schneiderman & Sweta Maheshwari & Monica C. Pillon, 2025. "CryoEM structure of the SLFN14 endoribonuclease reveals insight into RNA binding and cleavage," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    3. Xin Yong & Guowen Jia & Qin Yang & Chunzhuang Zhou & Sitao Zhang & Huaqing Deng & Daniel D. Billadeau & Zhaoming Su & Da Jia, 2025. "Cryo-EM structure of the BLOC-3 complex provides insights into the pathogenesis of Hermansky-Pudlak syndrome," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    4. Daniel J. Diaz & Chengyue Gong & Jeffrey Ouyang-Zhang & James M. Loy & Jordan Wells & David Yang & Andrew D. Ellington & Alexandros G. Dimakis & Adam R. Klivans, 2024. "Stability Oracle: a structure-based graph-transformer framework for identifying stabilizing mutations," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Qianqian Ming & Daniel Antfolk & David A. Price & Anna Manturova & Elliot Medina & Srishti Singh & Charlotte Mason & Timothy H. Tran & Keiran S. M. Smalley & Daisy W. Leung & Vincent C. Luca, 2024. "Structural basis for mouse LAG3 interactions with the MHC class II molecule I-Ab," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    6. Julian O. Streit & Sammy H. S. Chan & Saifu Daya & John Christodoulou, 2025. "Rational design of 19F NMR labelling sites to probe protein structure and interactions," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    7. Max S. Kloet & Chatrin Chatrin & Rishov Mukhopadhyay & Bianca D. M. van Tol & Rebecca Smith & Sarah A. Rotman & Rayman T. N. Tjokrodirijo & Kang Zhu & Andrii Gorelik & Lucy Maginn & Paul R. Elliott & , 2025. "Identification of RNF114 as ADPr-Ub reader through non-hydrolysable ubiquitinated ADP-ribose," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    8. Paloma García Casas & Michela Rossini & Linnea Påvénius & Mezida Saeed & Nikita Arnst & Sonia Sonda & Tânia Fernandes & Irene D’Arsiè & Matteo Bruzzone & Valeria Berno & Andrea Raimondi & Maria Livia , 2024. "Simultaneous detection of membrane contact dynamics and associated Ca2+ signals by reversible chemogenetic reporters," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    9. William J. Nicolas & Anna Shiriaeva & Michael W. Martynowycz & Angus C. Grey & Yasmeen N. Ruma & Paul J. Donaldson & Tamir Gonen, 2025. "Structure of the lens MP20 mediated adhesive junction," Nature Communications, Nature, vol. 16(1), pages 1-10, December.
    10. Cornelia Sala & Martin Würtz & Enrico Salvatore Atorino & Annett Neuner & Patrick Partscht & Thomas Hoffmann & Sebastian Eustermann & Elmar Schiebel, 2024. "An interaction network of inner centriole proteins organised by POC1A-POC1B heterodimer crosslinks ensures centriolar integrity," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    11. Tae-Kyeong Jeong & R. Ciaran MacKenzie Frater & Jongha Yoon & Anja Groth & Ji-Joon Song, 2025. "CODANIN-1 sequesters ASF1 by using a histone H3 mimic helix to regulate the histone supply," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    12. Jianan Zhang & Yuko Tsutsui & Hengyi Li & Tongqing Li & Yueyue Wang & Salma Laraki & Sofia Alarcon-Frias & Steven E. Stayrook & Daryl E. Klein, 2025. "Structural basis for the interaction between the Drosophila RTK Sevenless (dROS1) and the GPCR BOSS," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    13. James Hodgkinson-Bean & Rafael Ayala & Nadishka Jayawardena & Georgia L. Rutter & Bridget N. J. Watson & David Mayo-Muñoz & James Keal & Peter C. Fineran & Matthias Wolf & Mihnea Bostina, 2025. "Global structural survey of the flagellotropic myophage φTE infecting agricultural pathogen Pectobacterium atrosepticum," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    14. Huiyu Cai & Zuobai Zhang & Mingkai Wang & Bozitao Zhong & Quanxiao Li & Yuxuan Zhong & Yanling Wu & Tianlei Ying & Jian Tang, 2024. "Pretrainable geometric graph neural network for antibody affinity maturation," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    15. Timothy K. Soh & Sofia Ognibene & Saskia Sanders & Robin Schäper & Benedikt B. Kaufer & Jens B. Bosse, 2024. "A proteome-wide structural systems approach reveals insights into protein families of all human herpesviruses," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    16. Nathalie Béchon & Nitzan Tal & Avigail Stokar-Avihail & Alon Savidor & Meital Kupervaser & Sarah Melamed & Gil Amitai & Rotem Sorek, 2024. "Diversification of molecular pattern recognition in bacterial NLR-like proteins," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    17. Amika Singla & Daniel J. Boesch & Ho Yee Joyce Fung & Chigozie Ngoka & Avery S. Enriquez & Ran Song & Daniel A. Kramer & Yan Han & Esther Banarer & Andrew Lemoff & Puneet Juneja & Daniel D. Billadeau , 2024. "Structural basis for Retriever-SNX17 assembly and endosomal sorting," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    18. Bevika Sewgoolam & Kin Ki Jim & Vincent de Bakker & Florian P. Bock & Paddy S. Gibson & Jan-Willem Veening, 2025. "Genome-wide antibiotic-CRISPRi profiling identifies LiaR activation as a strategy to resensitize fluoroquinolone-resistant Streptococcus pneumoniae," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    19. Daniel R. Fox & Kazem Asadollahi & Imogen Samuels & Bradley A. Spicer & Ashleigh Kropp & Christopher J. Lupton & Kevin Lim & Chunxiao Wang & Hari Venugopal & Marija Dramicanin & Gavin J. Knott & Rhys , 2025. "Inhibiting heme piracy by pathogenic Escherichia coli using de novo-designed proteins," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    20. Stephen A. Rettie & Katelyn V. Campbell & Asim K. Bera & Alex Kang & Simon Kozlov & Yensi Flores Bueso & Joshmyn Cruz & Maggie Ahlrichs & Suna Cheng & Stacey R. Gerben & Mila Lamb & Analisa Murray & V, 2025. "Cyclic peptide structure prediction and design using AlphaFold2," Nature Communications, Nature, vol. 16(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51776-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.