In silico Characterization of a Hypothetical Protein (PBJ89160.1) from Neisseria meningitidis Exhibits a New Insight on Nutritional Virulence and Molecular Docking to Uncover a Therapeutic Target.

Autor: Asha IJ; Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh., Gupta SD; Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh., Hossain MM; Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh., Islam MN; Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh., Akter NN; Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh., Islam MM; Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh., Das SC; Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh., Barman DN; Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh.
Jazyk: angličtina
Zdroj: Evolutionary bioinformatics online [Evol Bioinform Online] 2024 Nov 11; Vol. 20, pp. 11769343241298307. Date of Electronic Publication: 2024 Nov 11 (Print Publication: 2024).
DOI: 10.1177/11769343241298307
Abstrakt: Objective: Neisseria meningitidis is an encapsulated, diplococcus, kidney bean-shaped bacteria that causes bacterial meningitis. Our study hopes to advance our understanding of disease progression, the spread frequency of the bacteria in people, and the interactions between the bacteria and human body by identifying a functional protein, potentially serving as a target for meningococcal medicine in the future.
Methods: A hypothetical protein HP (PBJ89160.1) from N.   meningitidis was employed in this study for extensive structural and functional characterization. In the predictive functional role of HP, several constitutive bioinformatics approaches are applied, such as prediction of physiological properties, domain and motif family function, secondary and tertiary structure prediction, energy minimization, quality validation, docking, and ADMET analysis. To create the protein's three-dimensional (3D) structure, a template protein (PDB_ID: 3GXA) is used with 99% sequence identity by homology modeling technique with the HHpred server. To mitigate the pathogenicity associated with the HP function, it was docked with the natural ligand methionine and five other drug compounds like Verapamil, Loperamide, Thioridazine, Chlorpromazine, and Auranofine.
Results: The protein is predicted to be acidic, soluble and hydrophilic by physicochemical properties analysis. Subcellular localization analysis demonstrated the protein to be periplasmic. The HP has an ATP-binding cassette transporter (also known as ABC transporter) involved in uptake of methionine (MetQ) that creates nutritional virulence in host. Energy minimization, multiple quality assessments, and validation value determination led to the conclusion that the HP model had a workable and acceptable quality. Following ADMET analysis and binding affinity assessments from the docking studies, Loperamide emerged as the most promising therapeutic compound, effectively inhibiting the ATP transporter activity of the HP.
Conclusion: Comparative genomic analysis revealed that this protein is specific to N. meningitidis and has no homologs in human proteins, thereby identifying it as a potential target for therapeutic intervention.
Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
(© The Author(s) 2024.)
Databáze: MEDLINE
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