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

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

doi:10.1039/d0ra09555a

Cited by 27 publications

(42 citation statements)

References 61 publications

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“…Currently, complex structures of up to 1000 residues are registered in FMODB (7BV2, 1057 fragment). Among the FMO calculations performed by ABINIT-MP so far, the largest-sized protein is the trimer of S protein (3,300 residues) 48 , which is currently under preparation for registration for both open and closed structures. In the near future, we shall perform FMO calculations for large complex systems, such as RTCs of RdRp, including Helicase, nsp1-robosomal subunit, and Spike trimer-antibody, and elucidate the molecular recognition mechanism in these complex systems.…”

Section: Discussionmentioning

confidence: 99%

Special feature of COVID-19 in FMODB: Fragment molecular orbital calculations and interaction energy analysis of SARS-CoV-2 related proteins

Fukuzawa

Kato

Watanabe

et al. 2021

Preprint

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SARS-CoV-2 is the causative agent of coronavirus(known as , the virus causing the current pandemic. there are ongoing researches to develop effective therapeutics and vaccines against COVID-19 using various methods, and many results have been published.The structure-based drug design of SARS-CoV-2 related proteins is promising. However, 2 reliable information regarding the structural and intra-and intermolecular interactions is required. We have conducted studies based on the fragment molecular orbital (FMO) method for calculating the electronic structure of protein complexes and analyzing their quantitative molecular interactions. This enables us to extensively analyze the molecular interactions in residues or functional group units acting inside protein complexes. Such precise interaction data are available in the FMO database (FMODB) (https://drugdesign.riken.jp/FMODB/). Since April 2020, we have performed several FMO calculations on the structures of SARS-CoV-2 related proteins registered in the Protein Data Bank. We have published the results of 681 structures, including three structural proteins and eleven nonstructural proteins, on the COVID-19 special page (as of June 8, 2021). In this paper, we describe the entire COVID-19 special page of FMODB and discuss the calculation results for various proteins. These data not only aid the interpretation of experimentally determined structures but also the understanding of protein functions, which is useful for rational drug design for COVID-19.

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Section: Discussionmentioning

confidence: 99%

Special feature of COVID-19 in FMODB: Fragment molecular orbital calculations and interaction energy analysis of SARS-CoV-2 related proteins

Fukuzawa

Kato

Watanabe

et al. 2021

Preprint

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“…Interaction analyses between S-protein and hACE2 or B38 Fab antibodies using the FMO method have been reported [45][46][47] . This study focused on 12 antibodies/peptides (LCB1 27 , LCB3 27 , C105 23 , COVA2-04 21 , BD-604 26 , CB6 17 , B38 17 , BD-629 26 , C102 22 , CC12.3 19 , CC12.1 19 , and CV30 17 ) and analyzed the interactions between these antibodies/peptides and the RBD using the FMO method.…”

Section: Toc Graphicmentioning

confidence: 99%

Intermolecular Interaction Analyses on SARS-CoV-2 Receptor Binding Domain and Human Angiotensin-Converting Enzyme 2 Receptor-Blocking Antibody/peptide Using Fragment Molecular Orbital Calculation

Watanabe¹,

Watanabe²,

Honma³

et al. 2021

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<p>The spike glycoprotein (S-protein) mediates SARS-CoV-2 entry via intermolecular interaction with human angiotensin-converting enzyme 2 (hACE2). The receptor-binding domain (RBD) of the S-protein has been considered critical for this interaction and acts as the target of numerous neutralizing antibodies and antiviral peptides. This study used the fragment molecular orbital (FMO) method to analyze the interactions between RBD and antibodies/peptides and extracted crucial residues that can be used to epitopes. The interactions evaluated as inter-fragment interaction energy (IFIE) values between the RBD and 12 antibodies/peptides showed a fairly good correlation with the experimental activity pIC<sub>50</sub> (<i>R</i><sup>2</sup> = 0.540). Nine residues (T415, K417, Y421, F456, A475, F486, N487, N501, and Y505) were confirmed as crucial. Pair interaction energy decomposition analyses (PIEDA) showed that hydrogen bonds, electrostatic interactions, and π-orbital interactions are important. Our results provide essential information for understanding SARS-CoV-2-antibodies/peptide binding and may play roles in future antibody/antiviral drug design. </p>

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“…Coronavirus disease 2019 (COVID- 19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a pandemic by the World Health Organization and has caused worldwide social and economic problems. 1 Despite its signicant infectious strength and the worldwide research efforts, to date, no specic treatment has been established against this new virus.…”

Section: Introductionmentioning

confidence: 99%

“…3,[9][10][11][12][13] Analyses of molecular recognition hots spots between the SARS-CoV-2 S-protein and ACE2 were conducted by several computational simulations, including electrostatic potential, 14,15 molecular mechanics (MM)-based interaction energy analysis with classical force eld, 16 and quantum mechanics (QM)-based interaction energy analysis with or without evaluation of semiempirical dispersion energy. [17][18][19] Molecular dynamics (MD) simulations for the complex formed by the Sprotein and ACE2 were conducted to better understand their association. [20][21][22][23][24][25][26] Approaches for drug/neutralizing antibody design targeting S-protein have been reported, such as a de novo design peptide inhibitors for SARS-CoV-2, 27,28 a virtual screening of antiviral compounds for the SARS-CoV-2 ( ref.…”

Section: Introductionmentioning

confidence: 99%

“…[40][41][42] In recent years, the FMO method has been widely used as a drug discovery tool. 35,[43][44][45][46][47][48][49][50][51][52] Recent studies have also provided detailed information on the underlying antigen-antibody or ligand-binding characteristics of several drug-targeted proteins, main protease, [53][54][55] ribonucleic acid (RNA)-dependent RNA polymerase, 56 S-protein, 17,19 in COVID-19. To date, the FMO method has been successfully used for identifying key amino acid residues and sugar chains for PPI, such as molecular recognition for an inuenza hemagglutinin of a fragment antigen-binding (Fab) antibody [57][58][59][60][61][62][63][64][65][66][67] and a measles hemagglutinin of a signaling lymphocytic activation molecule.…”

Section: Introductionmentioning

confidence: 99%

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

Watanabe

Okiyama²,

Tanaka³

et al. 2020

Preprint

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<div>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. </div><div><br></div>

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

Abstract: Visualized IFIE results seen from chain-B of spike protein.

Cited by 27 publications

References 61 publications

Special feature of COVID-19 in FMODB: Fragment molecular orbital calculations and interaction energy analysis of SARS-CoV-2 related proteins

Special feature of COVID-19 in FMODB: Fragment molecular orbital calculations and interaction energy analysis of SARS-CoV-2 related proteins

Intermolecular Interaction Analyses on SARS-CoV-2 Receptor Binding Domain and Human Angiotensin-Converting Enzyme 2 Receptor-Blocking Antibody/peptide Using Fragment Molecular Orbital Calculation

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

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