Molecular recognition of SARS-CoV-2 spike glycoprotein: quantum chemical hot spot and epitope analyses
- ️Teruki Honma
* Corresponding authors
a
Center for Biosystems Dynamics Research, RIKEN, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
E-mail:
chiduru.watanabe@riken.jp
Fax: +81-45-503-9432
Tel: +81-45-503-9551
b JST, PRESTO, 4-1-8, Honcho, Kawaguchi, Saitama 332-0012, Japan
c Division of Medicinal Safety Science, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-9501, Japan
d Department of Computational Science, Graduate School of System Informatics, Kobe University, 1-1 Rokkodai, Nada-ku, Kobe, Hyogo 657-8501, Japan
e School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
f Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, 6-6-11 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8579, Japan
Abstract
Due to the COVID-19 pandemic, researchers have attempted to identify complex structures of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (S-protein) with angiotensin-converting enzyme 2 (ACE2) or a blocking antibody. However, the molecular recognition mechanism—critical information for drug and antibody design—has not been fully clarified at the amino acid residue level. Elucidating such a microscopic mechanism in detail requires a more accurate molecular interpretation that includes quantum mechanics to quantitatively evaluate hydrogen bonds, XH/π interactions (X = N, O, and C), and salt bridges. In this study, we applied the fragment molecular orbital (FMO) method to characterize the SARS-CoV-2 S-protein binding interactions with not only ACE2 but also the B38 Fab antibody involved in ACE2-inhibitory binding. By analyzing FMO-based interaction energies along a wide range of binding interfaces carefully, we identified amino acid residues critical for molecular recognition between S-protein and ACE2 or B38 Fab antibody. Importantly, hydrophobic residues that are involved in weak interactions such as CH–O hydrogen bond and XH/π interactions, as well as polar residues that construct conspicuous hydrogen bonds, play important roles in molecular recognition and binding ability. Moreover, through these FMO-based analyses, we also clarified novel hot spots and epitopes that had been overlooked in previous studies by structural and molecular mechanical approaches. Altogether, these hot spots/epitopes identified between S-protein and ACE2/B38 Fab antibody may provide useful information for future antibody design, evaluation of the binding property of the SARS-CoV-2 variants including its N501Y, and small or medium drug design against the SARS-CoV-2.
- This article is part of the themed collections: Coronavirus articles - free to access collection and Most popular 2021 chemical biology articles
Supplementary files
Article information
- https://doi.org/10.1039/D0SC06528E
- Edge Article
- 27 Nov 2020
- 21 Feb 2021
- 02 Mar 2021
-
DOI
Article type
Submitted
Accepted
First published
All publication charges for this article have been paid for by the Royal Society of Chemistry
Chem. Sci., 2021,12, 4722-4739
Permissions
Molecular recognition of SARS-CoV-2 spike glycoprotein: quantum chemical hot spot and epitope analyses
C. Watanabe, Y. Okiyama, S. Tanaka, K. Fukuzawa and T. Honma, Chem. Sci., 2021, 12, 4722 DOI: 10.1039/D0SC06528E
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