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

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,...

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Autores principales:	Abdur Rehman, Xiukang Wang, Sajjad Ahmad, Farah Shahid, Sidra Aslam, Usman Ali Ashfaq, Faris Alrumaihi, Muhammad Qasim, Abeer Hashem, Amal A. Al-Hazzani, Elsayed Fathi Abd_Allah
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Streptococcus pyogenes</i> multidrug resistance cross-resistance phytochemicals inhibitors pathogenic Medicine R
Acceso en línea:	https://doaj.org/article/7a074f5f29ea4946af135ffc115a6480
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spelling	oai:doaj.org-article:7a074f5f29ea4946af135ffc115a64802021-11-11T16:29:14ZIn Silico Core Proteomics and Molecular Docking Approaches for the Identification of Novel Inhibitors against <i>Streptococcus pyogenes</i>10.3390/ijerph1821113551660-46011661-7827https://doaj.org/article/7a074f5f29ea4946af135ffc115a64802021-10-01T00:00:00Zhttps://www.mdpi.com/1660-4601/18/21/11355https://doaj.org/toc/1661-7827https://doaj.org/toc/1660-4601<i>Streptococcus pyogenes</i> 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 <i>S. pyogenes</i> strains, making them more dangerous and pathogenic. Hence, it is necessary to identify and develop therapeutic methods that would present novel approaches to <i>S. pyogenes</i> infections. In the current study, a subtractive proteomics approach was employed to core proteomes of four strains of <i>S. pyogenes</i> 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 <i>S. pyogenes</i> infections.Abdur RehmanXiukang WangSajjad AhmadFarah ShahidSidra AslamUsman Ali AshfaqFaris AlrumaihiMuhammad QasimAbeer HashemAmal A. Al-HazzaniElsayed Fathi Abd_AllahMDPI AGarticle<i>Streptococcus pyogenes</i>multidrug resistancecross-resistancephytochemicalsinhibitorspathogenicMedicineRENInternational Journal of Environmental Research and Public Health, Vol 18, Iss 11355, p 11355 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Streptococcus pyogenes</i> multidrug resistance cross-resistance phytochemicals inhibitors pathogenic Medicine R
spellingShingle	<i>Streptococcus pyogenes</i> multidrug resistance cross-resistance phytochemicals inhibitors pathogenic Medicine R Abdur Rehman Xiukang Wang Sajjad Ahmad Farah Shahid Sidra Aslam Usman Ali Ashfaq Faris Alrumaihi Muhammad Qasim Abeer Hashem Amal A. Al-Hazzani Elsayed Fathi Abd_Allah In Silico Core Proteomics and Molecular Docking Approaches for the Identification of Novel Inhibitors against <i>Streptococcus pyogenes</i>
description	<i>Streptococcus pyogenes</i> 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 <i>S. pyogenes</i> strains, making them more dangerous and pathogenic. Hence, it is necessary to identify and develop therapeutic methods that would present novel approaches to <i>S. pyogenes</i> infections. In the current study, a subtractive proteomics approach was employed to core proteomes of four strains of <i>S. pyogenes</i> 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 <i>S. pyogenes</i> infections.
format	article
author	Abdur Rehman Xiukang Wang Sajjad Ahmad Farah Shahid Sidra Aslam Usman Ali Ashfaq Faris Alrumaihi Muhammad Qasim Abeer Hashem Amal A. Al-Hazzani Elsayed Fathi Abd_Allah
author_facet	Abdur Rehman Xiukang Wang Sajjad Ahmad Farah Shahid Sidra Aslam Usman Ali Ashfaq Faris Alrumaihi Muhammad Qasim Abeer Hashem Amal A. Al-Hazzani Elsayed Fathi Abd_Allah
author_sort	Abdur Rehman
title	In Silico Core Proteomics and Molecular Docking Approaches for the Identification of Novel Inhibitors against <i>Streptococcus pyogenes</i>
title_short	In Silico Core Proteomics and Molecular Docking Approaches for the Identification of Novel Inhibitors against <i>Streptococcus pyogenes</i>
title_full	In Silico Core Proteomics and Molecular Docking Approaches for the Identification of Novel Inhibitors against <i>Streptococcus pyogenes</i>
title_fullStr	In Silico Core Proteomics and Molecular Docking Approaches for the Identification of Novel Inhibitors against <i>Streptococcus pyogenes</i>
title_full_unstemmed	In Silico Core Proteomics and Molecular Docking Approaches for the Identification of Novel Inhibitors against <i>Streptococcus pyogenes</i>
title_sort	in silico core proteomics and molecular docking approaches for the identification of novel inhibitors against <i>streptococcus pyogenes</i>
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/7a074f5f29ea4946af135ffc115a6480
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In Silico Core Proteomics and Molecular Docking Approaches for the Identification of Novel Inhibitors against <i>Streptococcus pyogenes</i>

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