In Silico Core Proteomics and Molecular Docking Approaches for the Identification of Novel Inhibitors against Streptococcus pyogenes.

Abdur Rehman,Farah Shahid,Sajjad Ahmad,Abeer Hashem,Elsayed Fathi Abd_Allah,Xiukang Wang,Sidra Aslam,Usman Ali Ashfaq,Amal A Al-Hazzani,Faris Alrumaihi,Muhammad Qasim

doi:10.3390/ijerph182111355

Abdur Rehman, Farah Shahid + Show 9 more

Open Access

https://doi.org/10.3390/ijerph182111355

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Abstract

Streptococcus pyogenes is a significant pathogen that causes skin and upper respiratory tract infections and non-suppurative complications, such as acute rheumatic fever and post-strep glomerulonephritis. Multidrug resistance has emerged in S. pyogenes strains, making them more dangerous and pathogenic. Hence, it is necessary to identify and develop therapeutic methods that would present novel approaches to S. pyogenes infections. In the current study, a subtractive proteomics approach was employed to core proteomes of four strains of S. pyogenes using several bioinformatic software tools and servers. The core proteome consists of 1324 proteins, and 302 essential proteins were predicted from them. These essential proteins were analyzed using BLASTp against human proteome, and the number of potential targets was reduced to 145. Based on subcellular localization prediction, 46 proteins with cytoplasmic localization were chosen for metabolic pathway analysis. Only two cytoplasmic proteins, i.e., chromosomal replication initiator protein DnaA and two-component response regulator (TCR), were discovered to have the potential to be novel drug target candidates. Three-dimensional (3D) structure prediction of target proteins was carried out via the Swiss Model server. Molecular docking approach was employed to screen the library of 1000 phytochemicals against the interacting residues of the target proteins through the MOE software. Further, the docking studies were validated by running molecular dynamics simulation and highly popular binding free energy approaches of MM-GBSA and MM-PBSA. The findings revealed a promising candidate as a novel target against S. pyogenes infections.

Highlights

Introduction conditions of the Creative CommonsS. pyogenes is a catalase-negative, β-hemolytic, oxidase-negative, and Gram-positive streptococcus
Complete proteome of four strains of Streptococcus pyogenes—S. pyogenes serotype M1, S. pyogenes M1 476, S. pyogenes A20, and Streptococcus pyogenes serotype M3—were downloaded in the FASTA format from UniProt
The rapid emergence of antimicrobial resistance among Gram-positive bacteria has prompted the need to investigate novel drug targets that could aid in the development of new antimicrobial agents

Summary

Introduction

S. pyogenes is a catalase-negative, β-hemolytic, oxidase-negative, and Gram-positive streptococcus. It is called group A streptococcus (GAS). It forms pinpoint colonies at 5 to 10% CO2 [1]. S. pyogenes cells are non-motile and generally grow.

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