Interaction analyses of SARS-CoV-2 spike protein based on fragment molecular orbital calculations

Kazuki Akisawa; Ryo Hatada; Koji Okuwaki; Yuji Mochizuki; Kaori Fukuzawa; Yuto Komeiji; Shigenori Tanaka

doi:10.1039/D0RA09555A

Interaction analyses of SARS-CoV-2 spike protein based on fragment molecular orbital calculations†

Kazuki Akisawa,^a Ryo Hatada,^a Koji Okuwaki,

^a Yuji Mochizuki,

*^ab Kaori Fukuzawa,

^bcd Yuto Komeiji

^e and Shigenori Tanaka

^f

Author affiliations

* Corresponding authors

^a Department of Chemistry and Research Center for Smart Molecules, Faculty of Science, Rikkyo University, 3-34-1 Nishi-ikebukuro, Toshima-ku, Tokyo 171-8501, Japan
E-mail: fullmoon@rikkyo.ac.jp

^b Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan

^c School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

^d Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, 6-6-11 Aramaki, Aoba-ku, Sendai 980-8579, Japan

^e Health and Medical Research Institute, AIST, Tsukuba Central 6, Tsukuba, Ibaraki 305-8566, Japan

^f Graduate School of System Informatics, Department of Computational Science, Kobe University, 1-1 Rokkodai, Nada-ku, Kobe 657-8501, Japan

Abstract

At the stage of SARS-CoV-2 infection in human cells, the spike protein consisting of three chains, A, B, and C, with a total of 3300 residues plays a key role, and thus its structural properties and the binding nature of receptor proteins to host human cells or neutralizing antibodies has attracted considerable interest. Here, we report on interaction analyses of the spike protein in both closed (PDB-ID: 6VXX) and open (6VYB) structures, based on large-scale fragment molecular orbital (FMO) calculations at the level of up to the fourth-order Møller–Plesset perturbation with singles, doubles, and quadruples (MP4(SDQ)). Inter-chain interaction energies were evaluated for both structures, and a mutual comparison indicated considerable losses of stabilization energies in the open structure, especially in the receptor binding domain (RBD) of chain-B. The role of charged residues in inter-chain interactions was illuminated as well. By two separate calculations for the RBD complexes with angiotensin-converting enzyme 2 (ACE2) (6M0J) and B38 Fab antibody (7BZ5), it was found that the binding with ACE2 or antibody partially compensated for this stabilization loss of RBD.

This article is part of the themed collection: Coronavirus articles - free to access collection

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Interaction analyses of SARS-CoV-2 spike protein based on fragment molecular orbital calculations†

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Interaction analyses of SARS-CoV-2 spike protein based on fragment molecular orbital calculations

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