Machine Learning Reveals the Critical Interactions for SARS-CoV-2 Spike Protein Binding to ACE2

被引:37
|
作者
Pavlova, Anna [1 ]
Zhang, Zijian [1 ]
Acharya, Atanu [1 ]
Lynch, Diane L. [1 ]
Pang, Yui Tik [1 ]
Mou, Zhongyu [2 ]
Parks, Jerry M. [2 ]
Chipot, Chris [3 ,4 ]
Gumbart, James C. [1 ]
机构
[1] Georgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA
[2] Oak Ridge Natl Lab, Biosci Div, UT ORNL Ctr Mol Biophys, POB 2009, Oak Ridge, TN 37831 USA
[3] Lab Int Associe CNRS, F-54506 Vandoeuvre Les Nancy, France
[4] Univ Illinois, Dept Phys, Urbana, IL 61801 USA
来源
JOURNAL OF PHYSICAL CHEMISTRY LETTERS | 2021年 / 12卷 / 23期
基金
美国国家科学基金会;
关键词
SARS-CORONAVIRUS; RECEPTOR-BINDING; DYNAMICS; ADAPTATION;
D O I
10.1021/acs.jpclett.1c01494
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
SARS-CoV and SARS-CoV-2 bind to the human ACE2 receptor in practically identical conformations, although several residues of the receptor-binding domain (RBD) differ between them. Herein, we have used molecular dynamics (MD) simulations, machine learning (ML), and free-energy perturbation (FEP) calculations to elucidate the differences in binding by the two viruses. Although only subtle differences were observed from the initial MD simulations of the two RBD-ACE2 complexes, ML identified the individual residues with the most distinctive ACE2 interactions, many of which have been highlighted in previous experimental studies. FEP calculations quantified the corresponding differences in binding free energies to ACE2, and examination of MD trajectories provided structural explanations for these differences. Lastly, the energetics of emerging SARS-CoV-2 mutations were studied, showing that the affinity of the RBD for ACE2 is increased by N501Y and E484K mutations but is slightly decreased by K417N.
引用
收藏
页码:5494 / 5502
页数:9
相关论文
共 50 条
  • [41] Spike protein recognition of mammalian ACE2 predicts the host range and an optimized ACE2 for SARS-CoV-2 infection
    Luan, Junwen
    Lu, Yue
    Jin, Xiaolu
    Zhang, Leiliang
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2020, 526 (01) : 165 - 169
  • [42] Dynamics of the ACE2–SARS-CoV-2/SARS-CoV spike protein interface reveal unique mechanisms
    Amanat Ali
    Ranjit Vijayan
    Scientific Reports, 10
  • [43] Structural Changes at the Zinc Active Site of ACE2 on Binding the SARS-CoV-2 Spike Protein Receptor Binding Domain
    Dolgova, Natalia V.
    Qureshi, Muhammad
    Latimer, Matthew
    Grishin, Andrey
    Cygler, Miroslaw
    Vogt, Linda I.
    Cotelesage, Julien J. H.
    Sokaras, Dimosthenis
    Kroll, Thomas
    Pickering, Ingrid J.
    George, Graham N.
    INORGANIC CHEMISTRY, 2025, 64 (08) : 3831 - 3841
  • [44] Critical Point Mutations in the RBD of SARS-COV-2 Involved in Binding to ACE2
    Tolouie, Milad
    Farajnia, Safar
    Farajzadeh, Davoud
    Rahbarnia, Leila
    Saray, Ali Rabbizadeh
    MOLECULAR GENETICS MICROBIOLOGY AND VIROLOGY, 2024, 39 (01) : 86 - 94
  • [45] Structural basis for the different states of the spike protein of SARS-CoV-2 in complex with ACE2
    Yan, Renhong
    Zhang, Yuanyuan
    Li, Yaning
    Ye, Fangfei
    Guo, Yingying
    Xia, Lu
    Zhong, Xinyue
    Chi, Ximin
    Zhou, Qiang
    CELL RESEARCH, 2021, 31 (06) : 717 - 719
  • [46] Molecular modeling of the interaction of ligands with ACE2–SARS-CoV-2 spike protein complex
    Meden F. Isaac-Lam
    In Silico Pharmacology, 9 (1)
  • [47] Endothelial glycocalyx shields the interaction of SARS-CoV-2 spike protein with ACE2 receptors
    Marta Targosz-Korecka
    Agata Kubisiak
    Damian Kloska
    Aleksandra Kopacz
    Anna Grochot-Przeczek
    Marek Szymonski
    Scientific Reports, 11
  • [48] The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins
    Conceicao, Carina
    Thakur, Nazia
    Human, Stacey
    Kelly, James T.
    Logan, Leanne
    Bialy, Dagmara
    Bhat, Sushant
    Stevenson-Leggett, Phoebe
    Zagrajek, Adrian K.
    Hollinghurst, Philippa
    Varga, Michal
    Tsirigoti, Christina
    Tully, Matthew
    Chiu, Chris
    Moffat, Katy
    Silesian, Adrian Paul
    Hammond, John A.
    Maier, Helena J.
    Bickerton, Erica
    Shelton, Holly
    Dietrich, Isabelle
    Graham, Stephen C.
    Bailey, Dalan
    PLOS BIOLOGY, 2020, 18 (12)
  • [49] Endothelial glycocalyx shields the interaction of SARS-CoV-2 spike protein with ACE2 receptors
    Targosz-Korecka, Marta
    Kubisiak, Agata
    Kloska, Damian
    Kopacz, Aleksandra
    Grochot-Przeczek, Anna
    Szymonski, Marek
    SCIENTIFIC REPORTS, 2021, 11 (01)
  • [50] Perindopril Reduce SARS-COV-2 Spike-ACE2 Binding, ACE2 Overexpression and Cytokine Storm in Adipocyte Cell Infected with SARS-COV-2
    Al Farabi, M. J. Makhyan Jibril
    Hermawan, H. O. Hanestya Oky
    Harsoyo, P. M. H. Primasitha Maharani
    Drakos, S. G. D. Stavros George
    Suryawan, I. G. R. I. Gde Rurus
    Ardiana, M. A. Meity
    EUROPEAN HEART JOURNAL, 2023, 44 : 151 - 151