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Hot spot profiles of SARS-CoV-2 and human ACE2 receptor protein protein interaction obtained by density functional tight binding fragment molecular orbital method.
Sci Rep. 2020 10 08; 10(1):16862.SR

Abstract

The prevalence of a novel β-coronavirus (SARS-CoV-2) was declared as a public health emergency of international concern on 30 January 2020 and a global pandemic on 11 March 2020 by WHO. The spike glycoprotein of SARS-CoV-2 is regarded as a key target for the development of vaccines and therapeutic antibodies. In order to develop anti-viral therapeutics for SARS-CoV-2, it is crucial to find amino acid pairs that strongly attract each other at the interface of the spike glycoprotein and the human angiotensin-converting enzyme 2 (hACE2) complex. In order to find hot spot residues, the strongly attracting amino acid pairs at the protein-protein interaction (PPI) interface, we introduce a reliable inter-residue interaction energy calculation method, FMO-DFTB3/D/PCM/3D-SPIEs. In addition to the SARS-CoV-2 spike glycoprotein/hACE2 complex, the hot spot residues of SARS-CoV-1 spike glycoprotein/hACE2 complex, SARS-CoV-1 spike glycoprotein/antibody complex, and HCoV-NL63 spike glycoprotein/hACE2 complex were obtained using the same FMO method. Following this, a 3D-SPIEs-based interaction map was constructed with hot spot residues for the hACE2/SARS-CoV-1 spike glycoprotein, hACE2/HCoV-NL63 spike glycoprotein, and hACE2/SARS-CoV-2 spike glycoprotein complexes. Finally, the three 3D-SPIEs-based interaction maps were combined and analyzed to find the consensus hot spots among the three complexes. As a result of the analysis, two hot spots were identified between hACE2 and the three spike proteins. In particular, E37, K353, G354, and D355 of the hACE2 receptor strongly interact with the spike proteins of coronaviruses. The 3D-SPIEs-based map would provide valuable information to develop anti-viral therapeutics that inhibit PPIs between the spike protein of SARS-CoV-2 and hACE2.

Authors+Show Affiliations

Department of Biotechnology, Yonsei University, Seoul, Republic of Korea. The Interdisciplinary Graduate Program in Integrative Biotechnology and Translational Medicine, Yonsei University, Incheon, Republic of Korea. Bioinformatics and Molecular Design Research Center (BMDRC), Incheon, Republic of Korea.Bioinformatics and Molecular Design Research Center (BMDRC), Incheon, Republic of Korea.Department of Biotechnology, Yonsei University, Seoul, Republic of Korea. Bioinformatics and Molecular Design Research Center (BMDRC), Incheon, Republic of Korea.Department of Biotechnology, Yonsei University, Seoul, Republic of Korea. Bioinformatics and Molecular Design Research Center (BMDRC), Incheon, Republic of Korea.Department of Biotechnology, Yonsei University, Seoul, Republic of Korea.Pharos I&BT Co., Ltd., Anyang-si, Gyeonggi-do, Republic of Korea.Pharos I&BT Co., Ltd., Anyang-si, Gyeonggi-do, Republic of Korea.Department of Biotechnology, Yonsei University, Seoul, Republic of Korea. ktno@yonsei.ac.kr. The Interdisciplinary Graduate Program in Integrative Biotechnology and Translational Medicine, Yonsei University, Incheon, Republic of Korea. ktno@yonsei.ac.kr. Bioinformatics and Molecular Design Research Center (BMDRC), Incheon, Republic of Korea. ktno@yonsei.ac.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33033344

Citation

Lim, Hocheol, et al. "Hot Spot Profiles of SARS-CoV-2 and Human ACE2 Receptor Protein Protein Interaction Obtained By Density Functional Tight Binding Fragment Molecular Orbital Method." Scientific Reports, vol. 10, no. 1, 2020, p. 16862.
Lim H, Baek A, Kim J, et al. Hot spot profiles of SARS-CoV-2 and human ACE2 receptor protein protein interaction obtained by density functional tight binding fragment molecular orbital method. Sci Rep. 2020;10(1):16862.
Lim, H., Baek, A., Kim, J., Kim, M. S., Liu, J., Nam, K. Y., Yoon, J., & No, K. T. (2020). Hot spot profiles of SARS-CoV-2 and human ACE2 receptor protein protein interaction obtained by density functional tight binding fragment molecular orbital method. Scientific Reports, 10(1), 16862. https://doi.org/10.1038/s41598-020-73820-8
Lim H, et al. Hot Spot Profiles of SARS-CoV-2 and Human ACE2 Receptor Protein Protein Interaction Obtained By Density Functional Tight Binding Fragment Molecular Orbital Method. Sci Rep. 2020 10 8;10(1):16862. PubMed PMID: 33033344.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hot spot profiles of SARS-CoV-2 and human ACE2 receptor protein protein interaction obtained by density functional tight binding fragment molecular orbital method. AU - Lim,Hocheol, AU - Baek,Ayoung, AU - Kim,Jongwan, AU - Kim,Min Sung, AU - Liu,Jiaxin, AU - Nam,Ky-Youb, AU - Yoon,JeongHyeok, AU - No,Kyoung Tai, Y1 - 2020/10/08/ PY - 2020/04/14/received PY - 2020/09/08/accepted PY - 2020/10/9/entrez PY - 2020/10/10/pubmed PY - 2020/10/28/medline SP - 16862 EP - 16862 JF - Scientific reports JO - Sci Rep VL - 10 IS - 1 N2 - The prevalence of a novel β-coronavirus (SARS-CoV-2) was declared as a public health emergency of international concern on 30 January 2020 and a global pandemic on 11 March 2020 by WHO. The spike glycoprotein of SARS-CoV-2 is regarded as a key target for the development of vaccines and therapeutic antibodies. In order to develop anti-viral therapeutics for SARS-CoV-2, it is crucial to find amino acid pairs that strongly attract each other at the interface of the spike glycoprotein and the human angiotensin-converting enzyme 2 (hACE2) complex. In order to find hot spot residues, the strongly attracting amino acid pairs at the protein-protein interaction (PPI) interface, we introduce a reliable inter-residue interaction energy calculation method, FMO-DFTB3/D/PCM/3D-SPIEs. In addition to the SARS-CoV-2 spike glycoprotein/hACE2 complex, the hot spot residues of SARS-CoV-1 spike glycoprotein/hACE2 complex, SARS-CoV-1 spike glycoprotein/antibody complex, and HCoV-NL63 spike glycoprotein/hACE2 complex were obtained using the same FMO method. Following this, a 3D-SPIEs-based interaction map was constructed with hot spot residues for the hACE2/SARS-CoV-1 spike glycoprotein, hACE2/HCoV-NL63 spike glycoprotein, and hACE2/SARS-CoV-2 spike glycoprotein complexes. Finally, the three 3D-SPIEs-based interaction maps were combined and analyzed to find the consensus hot spots among the three complexes. As a result of the analysis, two hot spots were identified between hACE2 and the three spike proteins. In particular, E37, K353, G354, and D355 of the hACE2 receptor strongly interact with the spike proteins of coronaviruses. The 3D-SPIEs-based map would provide valuable information to develop anti-viral therapeutics that inhibit PPIs between the spike protein of SARS-CoV-2 and hACE2. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/33033344/Hot_spot_profiles_of_SARS_CoV_2_and_human_ACE2_receptor_protein_protein_interaction_obtained_by_density_functional_tight_binding_fragment_molecular_orbital_method_ L2 - https://doi.org/10.1038/s41598-020-73820-8 DB - PRIME DP - Unbound Medicine ER -