The Druggable Pocketome of Corynebacterium diphtheriae : A New Approach for in silico Putative Druggable Targets

Frontiers in Genetics
Syed Shah HassanVasco A C Azevedo

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 ge...Continue Reading

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Citations

Jul 6, 2021·Frontiers in Microbiology·Mariana Teixeira Dornelles PariseJan Baumbach

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Software Mentioned

DrugScore DS
CELLO LOcalization predictor
MODELLER
ProtParam
MHOLine
HMMTOP
CSA
FILTERS
Procheck
MHOLline

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