In silico identification and characterization of potential druggable targets among hypothetical proteins of Leptospira interrogans serovar Copenhageni: a comprehensive bioinformatics approach
Leptospirosis is one of the neglected zoonosis, affecting human and animal populations worldwide. Reliable effective therapeutics and concerns to look for more research into the molecular analysis of its genome is therefore needed. In the genomic pool of the Leptospira interrogans many hypothetical...
| Main Authors: | , , , , |
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| Format: | Article |
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Taylor and Francis
2022
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| Online Access: | http://psasir.upm.edu.my/id/eprint/101934/ |
| _version_ | 1848863671036411904 |
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| author | Siddiqui, Quratulain Mohd Ali, Mohd Shukuri Thean, Adam Chor Leow Oslan, Siti Nurbaya Mohd Shariff, Fairolniza |
| author_facet | Siddiqui, Quratulain Mohd Ali, Mohd Shukuri Thean, Adam Chor Leow Oslan, Siti Nurbaya Mohd Shariff, Fairolniza |
| author_sort | Siddiqui, Quratulain |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Leptospirosis is one of the neglected zoonosis, affecting human and animal populations worldwide. Reliable effective therapeutics and concerns to look for more research into the molecular analysis of its genome is therefore needed. In the genomic pool of the Leptospira interrogans many hypothetical proteins are still uncharacterized. In the current research, we performed extensive in silico analysis to prioritize the potential hypothetical proteins of L. interrogans serovar Copenhageni via stepwise reducing the available hypothetical proteins (Total 3606) of the assembly to only 15, based on non-homologous to homosapien, essential, functional, virulent, cellular localization. Out of them, only two proteins WP_000898918.1 (Hypothetical Protein 1) & WP_001014594.1 (Hypothetical Protein 2) were found druggable and involved in protein-protein interaction network. The 3 D structures of these two target proteins were predicted via ab initio homology modeling followed by structures refinement and validation, as no structures were available till date. The analysis also revealed that the functional domains, families and protein-protein interacting partners identified in both proteins are crucial for the survival of the bacteria. The binding cavities were predicted for both the proteins through blind and specific protein-ligand docking with their respective ligands and inhibitors and were found to be in accordance with the druggable sites predicted by DoGSiteScorer. The docking interactions were found within the active functional domains for both the proteins while for Hypothetical Protein 2, the same residues were involved in interactions with Cytidine-5'-triphosphate in blind and specific docking. Furthermore, the simulations of molecular dynamics and free binding energy revealed the stable substrate binding and efficient binding energies, and were in accordance to our docking results. The work predicted two unique hypothetical proteins of L. interrogans as a potential druggable targets for designing of inhibitors for them. Communicated by Ramaswamy H. Sarma |
| first_indexed | 2025-11-15T13:36:37Z |
| format | Article |
| id | upm-101934 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-15T13:36:37Z |
| publishDate | 2022 |
| publisher | Taylor and Francis |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1019342023-07-11T04:23:58Z http://psasir.upm.edu.my/id/eprint/101934/ In silico identification and characterization of potential druggable targets among hypothetical proteins of Leptospira interrogans serovar Copenhageni: a comprehensive bioinformatics approach Siddiqui, Quratulain Mohd Ali, Mohd Shukuri Thean, Adam Chor Leow Oslan, Siti Nurbaya Mohd Shariff, Fairolniza Leptospirosis is one of the neglected zoonosis, affecting human and animal populations worldwide. Reliable effective therapeutics and concerns to look for more research into the molecular analysis of its genome is therefore needed. In the genomic pool of the Leptospira interrogans many hypothetical proteins are still uncharacterized. In the current research, we performed extensive in silico analysis to prioritize the potential hypothetical proteins of L. interrogans serovar Copenhageni via stepwise reducing the available hypothetical proteins (Total 3606) of the assembly to only 15, based on non-homologous to homosapien, essential, functional, virulent, cellular localization. Out of them, only two proteins WP_000898918.1 (Hypothetical Protein 1) & WP_001014594.1 (Hypothetical Protein 2) were found druggable and involved in protein-protein interaction network. The 3 D structures of these two target proteins were predicted via ab initio homology modeling followed by structures refinement and validation, as no structures were available till date. The analysis also revealed that the functional domains, families and protein-protein interacting partners identified in both proteins are crucial for the survival of the bacteria. The binding cavities were predicted for both the proteins through blind and specific protein-ligand docking with their respective ligands and inhibitors and were found to be in accordance with the druggable sites predicted by DoGSiteScorer. The docking interactions were found within the active functional domains for both the proteins while for Hypothetical Protein 2, the same residues were involved in interactions with Cytidine-5'-triphosphate in blind and specific docking. Furthermore, the simulations of molecular dynamics and free binding energy revealed the stable substrate binding and efficient binding energies, and were in accordance to our docking results. The work predicted two unique hypothetical proteins of L. interrogans as a potential druggable targets for designing of inhibitors for them. Communicated by Ramaswamy H. Sarma Taylor and Francis 2022-12-12 Article PeerReviewed Siddiqui, Quratulain and Mohd Ali, Mohd Shukuri and Thean, Adam Chor Leow and Oslan, Siti Nurbaya and Mohd Shariff, Fairolniza (2022) In silico identification and characterization of potential druggable targets among hypothetical proteins of Leptospira interrogans serovar Copenhageni: a comprehensive bioinformatics approach. Journal of Biomolecular Structure & Dynamics. pp. 1-21. ISSN 0739-1102; ESSN: 1538-0254 https://www.tandfonline.com/doi/abs/10.1080/07391102.2022.2154845?journalCode=tbsd20 10.1080/07391102.2022.2154845 |
| spellingShingle | Siddiqui, Quratulain Mohd Ali, Mohd Shukuri Thean, Adam Chor Leow Oslan, Siti Nurbaya Mohd Shariff, Fairolniza In silico identification and characterization of potential druggable targets among hypothetical proteins of Leptospira interrogans serovar Copenhageni: a comprehensive bioinformatics approach |
| title | In silico identification and characterization of potential druggable targets among hypothetical proteins of Leptospira interrogans serovar Copenhageni: a comprehensive bioinformatics approach |
| title_full | In silico identification and characterization of potential druggable targets among hypothetical proteins of Leptospira interrogans serovar Copenhageni: a comprehensive bioinformatics approach |
| title_fullStr | In silico identification and characterization of potential druggable targets among hypothetical proteins of Leptospira interrogans serovar Copenhageni: a comprehensive bioinformatics approach |
| title_full_unstemmed | In silico identification and characterization of potential druggable targets among hypothetical proteins of Leptospira interrogans serovar Copenhageni: a comprehensive bioinformatics approach |
| title_short | In silico identification and characterization of potential druggable targets among hypothetical proteins of Leptospira interrogans serovar Copenhageni: a comprehensive bioinformatics approach |
| title_sort | in silico identification and characterization of potential druggable targets among hypothetical proteins of leptospira interrogans serovar copenhageni: a comprehensive bioinformatics approach |
| url | http://psasir.upm.edu.my/id/eprint/101934/ http://psasir.upm.edu.my/id/eprint/101934/ http://psasir.upm.edu.my/id/eprint/101934/ |