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dc.contributor.author
Hassan, Syed S.
dc.contributor.author
Jamal, Syed B.
dc.contributor.author
Radusky, Leandro Gabriel
dc.contributor.author
Tiwari, Sandeep
dc.contributor.author
Ullah, Asad
dc.contributor.author
Ali, Javed
dc.contributor.author
Behramand, null
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de Carvalho, Paulo V. S. D.
dc.contributor.author
Shams, Rida
dc.contributor.author
Khan, Sabir
dc.contributor.author
Figueiredo, Henrique C. P.
dc.contributor.author
Barh, Debmalya
dc.contributor.author
Ghosh, Preetam
dc.contributor.author
Silva, Artur
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Baumbach, Jan
dc.contributor.author
Röttger, Richard
dc.contributor.author
Turjanski, Adrian
dc.contributor.author
Azevedo, Vasco A. C.
dc.date.available
2020-01-08T14:25:11Z
dc.date.issued
2018-02
dc.identifier.citation
Hassan, Syed S.; Jamal, Syed B.; Radusky, Leandro Gabriel; Tiwari, Sandeep; Ullah, Asad; et al.; The druggable pocketome of Corynebacterium diphtheriae: A new approach for in silico putative druggable targets; Frontiers Research Foundation; Frontiers in Genetics; 9; 44; 2-2018; 1-9
dc.identifier.issn
1664-8021
dc.identifier.uri
http://hdl.handle.net/11336/93934
dc.description.abstract
Diphtheria is an acute and highly infectious disease, previously regarded as endemic in nature but vaccine-preventable, is caused by Corynebacterium diphtheriae (Cd). In this work, we used an in silico approach along the 13 complete genome sequences of C. diphtheriae followed by a computational assessment of structural information of the binding sites to characterize the "pocketome druggability." To this end, we first computed the "modelome" (3D structures of a complete genome) of a randomly selected reference strain Cd NCTC13129; that had 13,763 open reading frames (ORFs) and resulted in 1,253 (~9%) structure models. The amino acid sequences of these modeled structures were compared with the remaining 12 genomes and consequently, 438 conserved protein sequences were obtained. The RCSB-PDB database was consulted to check the template structures for these conserved proteins and as a result, 401 adequate 3D models were obtained. We subsequently predicted the protein pockets for the obtained set of models and kept only the conserved pockets that had highly druggable (HD) values (137 across all strains). Later, an off-target host homology analyses was performed considering the human proteome using NCBI database. Furthermore, the gene essentiality analysis was carried out that gave a final set of 10-conserved targets possessing highly druggable protein pockets. To check the target identification robustness of the pipeline used in this work, we crosschecked the final target list with another in-house target identification approach for C. diphtheriae thereby obtaining three common targets, these were; hisE-phosphoribosyl-ATP pyrophosphatase, glpX-fructose 1,6-bisphosphatase II, and rpsH-30S ribosomal protein S8. Our predicted results suggest that the in silico approach used could potentially aid in experimental polypharmacological target determination in C. diphtheriae and other pathogens, thereby, might complement the existing and new drug-discovery pipelines.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Frontiers Research Foundation
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
CORYNEBACTERIUM DIPHTHERIA
dc.subject
DRUGGABLE GENOME
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GLOBAL DRUGGABLE (GD)
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HIGHLY DRUGGABLE (HD)
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POCKETOME
dc.subject
PUTATIVE THERAPEUTIC TARGETS
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STRUCTURAL PROTEOMICS
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Genética y Herencia
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Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
The druggable pocketome of Corynebacterium diphtheriae: A new approach for in silico putative druggable targets
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-10-21T19:46:44Z
dc.journal.volume
9
dc.journal.number
44
dc.journal.pagination
1-9
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Hassan, Syed S.. Consejo Nacional de Investigaciones Científicas y Técnicas. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Jamal, Syed B.. Consejo Nacional de Investigaciones Científicas y Técnicas. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Radusky, Leandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Tiwari, Sandeep. Consejo Nacional de Investigaciones Científicas y Técnicas. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Ullah, Asad. Consejo Nacional de Investigaciones Científicas y Técnicas. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Ali, Javed. Consejo Nacional de Investigaciones Científicas y Técnicas. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Behramand, null. Consejo Nacional de Investigaciones Científicas y Técnicas. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: de Carvalho, Paulo V. S. D.. Consejo Nacional de Investigaciones Científicas y Técnicas. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Shams, Rida. Consejo Nacional de Investigaciones Científicas y Técnicas. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Khan, Sabir. Consejo Nacional de Investigaciones Científicas y Técnicas. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Figueiredo, Henrique C. P.. Consejo Nacional de Investigaciones Científicas y Técnicas. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Barh, Debmalya. Consejo Nacional de Investigaciones Científicas y Técnicas. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Ghosh, Preetam. Consejo Nacional de Investigaciones Científicas y Técnicas. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Silva, Artur. Consejo Nacional de Investigaciones Científicas y Técnicas. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Baumbach, Jan. Consejo Nacional de Investigaciones Científicas y Técnicas. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Röttger, Richard. Consejo Nacional de Investigaciones Científicas y Técnicas. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Turjanski, Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
dc.description.fil
Fil: Azevedo, Vasco A. C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Universidad de Buenos Aires; Argentina
dc.journal.title
Frontiers in Genetics
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://journal.frontiersin.org/article/10.3389/fgene.2018.00044/full
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3389/fgene.2018.00044
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