Molecular Recognition of SARS-CoV-2 Spike Glycoprotein: Quantum Chemical Hot Spot and Epitope Analyses

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 inter-faces carefully, we identified amino acid residues critical for molecular recognition between S-protein and ACE2 or B38 Fab antibody. Importantly, hydrophobic residues that attribute to weak interactions such as CH-O 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 anti-body design and small or medium drug design against the SARS-CoV-2..

Medienart:

Preprint

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

chemRxiv.org - (2021) vom: 18. Nov. Zur Gesamtaufnahme - year:2021

Sprache:

Englisch

Beteiligte Personen:

Watanabe, Chiduru [VerfasserIn]
Okiyama, Yoshio [VerfasserIn]
Tanaka, Shigenori [VerfasserIn]
Fukuzawa, Kaori [VerfasserIn]
Honma, Teruki [VerfasserIn]

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Themen:

540
Chemistry

doi:

10.26434/chemrxiv.13200176

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

XCH019294174