Machine Learning Reveals the Critical Interactions for SARS-CoV-2 Spike Protein Binding to ACE2
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作者:
Pavlova, Anna
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Georgia Inst Technol, Sch Phys, Atlanta, GA 30332 USAGeorgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA
Pavlova, Anna
[1
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Zhang, Zijian
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Georgia Inst Technol, Sch Phys, Atlanta, GA 30332 USAGeorgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA
Zhang, Zijian
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Acharya, Atanu
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Georgia Inst Technol, Sch Phys, Atlanta, GA 30332 USAGeorgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA
Acharya, Atanu
[1
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Lynch, Diane L.
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Georgia Inst Technol, Sch Phys, Atlanta, GA 30332 USAGeorgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA
Lynch, Diane L.
[1
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Pang, Yui Tik
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Georgia Inst Technol, Sch Phys, Atlanta, GA 30332 USAGeorgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA
Pang, Yui Tik
[1
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Mou, Zhongyu
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Oak Ridge Natl Lab, Biosci Div, UT ORNL Ctr Mol Biophys, POB 2009, Oak Ridge, TN 37831 USAGeorgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA
Mou, Zhongyu
[2
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Parks, Jerry M.
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Oak Ridge Natl Lab, Biosci Div, UT ORNL Ctr Mol Biophys, POB 2009, Oak Ridge, TN 37831 USAGeorgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA
Parks, Jerry M.
[2
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Chipot, Chris
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Lab Int Associe CNRS, F-54506 Vandoeuvre Les Nancy, France
Univ Illinois, Dept Phys, Urbana, IL 61801 USAGeorgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA
Chipot, Chris
[3
,4
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Gumbart, James C.
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Georgia Inst Technol, Sch Phys, Atlanta, GA 30332 USAGeorgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA
Gumbart, James C.
[1
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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
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.
机构:
Shandong First Med Univ, Inst Basic Med, Shandong Prov Hosp, Jinan 250062, Shandong, Peoples R ChinaShandong First Med Univ, Inst Basic Med, Shandong Prov Hosp, Jinan 250062, Shandong, Peoples R China
Luan, Junwen
Lu, Yue
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Shandong First Med Univ, Inst Basic Med, Shandong Prov Hosp, Jinan 250062, Shandong, Peoples R China
Univ Jinan, Shandong Acad Med Sci, Sch Med & Life Sci, Jinan 250200, Shandong, Peoples R ChinaShandong First Med Univ, Inst Basic Med, Shandong Prov Hosp, Jinan 250062, Shandong, Peoples R China
Lu, Yue
Jin, Xiaolu
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机构:
Shandong First Med Univ, Inst Basic Med, Shandong Prov Hosp, Jinan 250062, Shandong, Peoples R China
Univ Jinan, Shandong Acad Med Sci, Sch Med & Life Sci, Jinan 250200, Shandong, Peoples R ChinaShandong First Med Univ, Inst Basic Med, Shandong Prov Hosp, Jinan 250062, Shandong, Peoples R China
Jin, Xiaolu
Zhang, Leiliang
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机构:
Shandong First Med Univ, Inst Basic Med, Shandong Prov Hosp, Jinan 250062, Shandong, Peoples R ChinaShandong First Med Univ, Inst Basic Med, Shandong Prov Hosp, Jinan 250062, Shandong, Peoples R China