RCSB Protein Data Bank: Enabling biomedical research and drug discovery

Goodsell, David S.; Zardecki, Christine; Costanzo, Luigi Di; Duarte, José M.; Hudson, Brian P.; Persikova, Irina; Segura, Joan; Shao, Chenghua; Voigt, Maria; Westbrook, John D.; Young, Jasmine; Burley, S.K.

doi:10.1002/pro.3730

Cited by 247 publications

(205 citation statements)

References 115 publications

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“…Structures of both the proteins were identified by PDB-BLAST and retrieved from RCSB protein data bank. 11 Data for genetic variants and allele frequencies were obtained from Ensembl Genome Browser 12 and gnomAD. 13 Appropriate filters were employed to limit the data to only the coding region variants of ACE2 gene.…”

Section: Data Mining For Structure and Genetic Polymorphismmentioning

confidence: 99%

Structural variations in human ACE2 may influence its binding with SARS‐CoV‐2 spike protein

Hussain

Jabeen

Raza

et al. 2020

Journal of Medical Virology

330

339

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The recent pandemic of COVID-19, caused by SARS-CoV-2, is unarguably the most fearsome compared with the earlier outbreaks caused by other coronaviruses, SARS-CoV and MERS-CoV. Human ACE2 is now established as a receptor for the SARS-CoV-2 spike protein. Where variations in the viral spike protein, in turn, lead to the cross-species transmission of the virus, genetic variations in the host receptor ACE2 may also contribute to the susceptibility and/or resistance against the viral infection. This study aims to explore the binding of the proteins encoded by different human ACE2 allelic variants with SARS-CoV-2 spike protein. Briefly, coding variants of ACE2 corresponding to the reported binding sites for its attachment with coronavirus spike protein were selected and molecular models of these variants were constructed by homology modeling. The models were then superimposed over the native ACE2 and ACE2-spike protein complex, to observe structural changes in the ACE2 variants and their intermolecular interactions with SARS-CoV-2 spike protein, respectively. Despite strong overall structural similarities, the spatial orientation of the key interacting residues varies in the ACE2 variants compared with the wildtype molecule. Most ACE2 variants showed a similar binding affinity for SARS-CoV-2 spike protein as observed in the complex structure of wild-type ACE2 and SARS-CoV-2 spike protein. However, ACE2 alleles, rs73635825 (S19P) and rs143936283 (E329G) showed noticeable variations in their intermolecular interactions with the viral spike protein. In summary, our data provide a structural basis of potential resistance against SARS-CoV-2 infection driven by ACE2 allelic variants.

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Section: Data Mining For Structure and Genetic Polymorphismmentioning

confidence: 99%

Structural variations in human ACE2 may influence its binding with SARS‐CoV‐2 spike protein

Hussain

Jabeen

Raza

et al. 2020

Journal of Medical Virology

330

339

View full text Add to dashboard Cite

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“…The structural data for biological assemblies of SARS-Cov-2 was downloaded from Coronavirus3D server developed recently by our group [13]. The Coronavirus3D server provides links to experimental structures of SARS-CoV-2 proteins stored in PDB [14] and models of protein regions of SARS-Cov-2 for which direct structural characterization is still lacking. Models were calculated with Modeller [35] based on FFAS [36] alignments.…”

Section: Structural Coverage Of the Sars-cov-2 Proteome And Derived Smentioning

confidence: 99%

“…In parallel to the genomic characterization of the SARS-CoV-2 virus, its proteins are being characterized structurally at an equally rapid pace [12], mostly as a part of the drug discovery effort, and, as of the end of June 2020, there is direct or indirect high-quality structural information for over 60% of the SARS-CoV-2 proteome. Our group has recently developed the coronavirus3D server [13], available at https://coronavirus3D.org, to integrate information about the three-dimensional structures of SARS-CoV-2 virus proteins from the Protein Data Bank (PDB) [14] resource (http://rcsb.org) with the information on SARS-CoV-2 genomic variations retrieved from the China National Center for Bioinformation (CNCB) website (https://bigd.big.ac.cn/ncov/variation). This integration allows us to track in real-time the emergence of new trends or patterns in the evolving SARS-CoV-2 genomes in the context of the structures of its proteins.…”

Section: Introductionmentioning

confidence: 99%

The interplay of SARS-CoV-2 evolution and constraints imposed by the structure and functionality of its proteins

Jaroszewski

Iyer

Alisoltani

et al. 2020

Preprint

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Fast evolution of the SARS-CoV-2 virus provides us with unique information about the patterns of genetic changes in a single pathogen in the timescale of months. This data is used extensively to track the phylodynamic of the pandemics spread and its split into distinct clades. Here we show that the patterns of SARS-CoV-2 virus mutations along its genome are closely correlated with the structural features of the coded proteins. We show that the foldability of proteins 3D structures and conservation of their functions are the universal factors driving evolutionary selection in protein-coding genes. Insights from the analysis of mutation distribution in the context of the SARS-CoV-2 proteins structures and functions have practical implications including evaluating potential antigen epitopes or selection of primers for PCR-based COVID-19 tests.

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“…Based on screening, top hit molecule was taken for molecular docking and MD Simulations. Through this, the binding affinity or change in binding free energy of newly formed drug-target complex was determined by simulations method and deviations measured on increasing temperature (Aaboud et al, 2018;Adasme-Carreno et al, 2014;Athir et al, 2019;Goodsell et al, 2020). Herein, MM-GBSA method was to calculate the change in enthalpy and the change in free energy for the formation of complex, number of hydrogen bonds (HBs) are determined to study the binding of the hit molecule with the protease of SARS-CoV-2 for COVID-19.…”

Section: Introductionmentioning

confidence: 99%

Understanding the binding affinity of noscapines with protease of SARS-CoV-2 for COVID-19 using MD simulations at different temperatures

Kumar

Kumari

Jayaraj

et al. 2020

Journal of Biomolecular Structure and Dynamics

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The current outbreak of a novel coronavirus, named as SARS-CoV-2 causing COVID-19 occurred in 2019, is in dire need of finding potential therapeutic agents. Recently, ongoing viral epidemic due to coronavirus (SARS-CoV-2) primarily affected mainland China that now threatened to spread to populations in most countries of the world. In spite of this, there is currently no antiviral drug/ vaccine available against coronavirus infection, COVID-19. In the present study, computer-aided drug design-based screening to find out promising inhibitors against the coronavirus (SARS-CoV-2) leads to infection, COVID-19. The lead therapeutic molecule was investigated through docking and molecular dynamics simulations. In this, binding affinity of noscapines(23B)-protease of SARS-CoV-2 complex was evaluated through MD simulations at different temperatures. Our research group has established that noscapine is a chemotherapeutic agent for the treatment of drug resistant cancers; however, noscapine was also being used as anti-malarial, anti-stroke and cough-suppressant. This study suggests for the first time that noscapine exerts its antiviral effects by inhibiting viral protein synthesis. ARTICLE HISTORY

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RCSB Protein Data Bank: Enabling biomedical research and drug discovery

Abstract: This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 247 publications

References 115 publications

Structural variations in human ACE2 may influence its binding with SARS‐CoV‐2 spike protein

Structural variations in human ACE2 may influence its binding with SARS‐CoV‐2 spike protein

The interplay of SARS-CoV-2 evolution and constraints imposed by the structure and functionality of its proteins

Understanding the binding affinity of noscapines with protease of SARS-CoV-2 for COVID-19 using MD simulations at different temperatures

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