Molecular recognition of SARS-CoV-2 spike glycoprotein: quantum chemical hot spot and epitope analyses

Watanabe, Chiduru; Okiyama, Yoshio; Tanaka, Shigenori; Fukuzawa, Kaori; Honma, Teruki

doi:10.1039/d0sc06528e

Cited by 45 publications

(63 citation statements)

References 82 publications

(148 reference statements)

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“…Previous research on the interaction between SARS-CoV-2 S-protein RBD and ACE2 with FMO calculation 46 also showed that the interaction sites of hACE2 on RBD could be concentrated in these two regions.…”

Section: Toc Graphicmentioning

confidence: 85%

“…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%

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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

Preprint

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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 pIC50 (R2 = 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.

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Section: Toc Graphicmentioning

confidence: 85%

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

Preprint

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“…On the other hand, the main contribution of Asn501 is ES with surrounding amino acid residues (Tyr41, Lys353, Gly354, etc.). In a previous study, it was reported that the N501Y mutation enhances the ability of S protein to bind to ACE2 by acquiring more hydrogen bonds and XH/ interactions than WT 49 .…”

Section: Spike (S) Proteinmentioning

confidence: 99%

“…Due to the large negative charge of ACE2, hydrogen bonds and XH/ interactions, which are key interactions in molecular recognition of S protein, are hidden by ES interactions of the charged residues. However, the hydrogen bond can be easily interpreted by analyzing the ES and CT terms of PIEDA, and the XH/ interaction can be easily interpreted by analyzing the DI term 49 . In addition, we performed PIEDA analysis of the mutant residues of S protein, Lys417 and Asn501, in the South African and Brazilian mutants and the surrounding residues (Figures 15 b,c).…”

Section: Spike (S) Proteinmentioning

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

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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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“…Weak hydrogen bonds (HBs) involving CH bonds as donor groups and O as acceptor atoms have been evidenced decades ago for crystalline organic molecules. [1][2][3] Since then, they have a recognized role in biology and in several areas of chemistry [4][5][6][7] thanks to their implications in molecular properties like crystal packing, [8,9] supramolecular assembly's formation, [10] conformational states, [8,11,12] host-guest interactions and molecular recognition, [13,14] organic-inorganic hybrid networks [15] and drug discovery [16] to name a few.…”

Section: Introductionmentioning

confidence: 99%

Ubiquitous Presence of Intermolecular CH…O Hydrogen Bonds in As‐synthesized Host‐Guest Zeolite Materials

et al. 2021

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CH⋅⋅⋅O hydrogen bonds (HBs) are ubiquituous in silica zeolite crystals hosting cationic Organic Structure Directing agents (OSDAs). This new finding is notably supported by a correlation between experimental CÀ O distances and COSi angles' distributions of two series of 19 and 11 available structures. The correlation enables to asses the directionality of the CH…O intermolecular interactions and to extrapolate a geometrical model for the hydrogen bonded moeities. DFTÀ D3 calculations on representative structures further confirmed the presence of these HBs and their geometry on the basis of HÀ O distances, CHO angles and electron density. The reported insights demonstrate also the particularities of these intermolecular interactions in terms of charge distribution and electrostatic potentials. Further, multiple hydrogen bonding is evidenced between OSDAs and zeolites' channels and cages, opening new perspectives in the study of zeolite-OSDA host-guest interactions.

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Molecular recognition of SARS-CoV-2 spike glycoprotein: quantum chemical hot spot and epitope analyses

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...

Cited by 45 publications

References 82 publications

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

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

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

Ubiquitous Presence of Intermolecular CH…O Hydrogen Bonds in As‐synthesized Host‐Guest Zeolite Materials

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