Structural and functional characterization of a unique hypothetical protein (WP_003901628.1) of Mycobacterium tuberculosis: a computational approach

Uddin, Reaz; Rafi, Sidra

doi:10.1007/s00044-017-1822-0

Cited by 9 publications

(5 citation statements)

References 61 publications

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“…This situation demonstrates the need to comprehend/improve the functional characterization processes of these proteins. In this context, we propose, as supported by the literature [ 255 , 257 , 258 , 262 , 263 , 264 , 265 , 266 ], one in silico workflow for functional prediction of hypothetical proteins ( Figure 3 ).…”

Section: Approaches Used To Search For New Diagnostic Candidatesmentioning

confidence: 84%

Challenges in Serologic Diagnostics of Neglected Human Systemic Mycoses: An Overview on Characterization of New Targets

et al. 2022

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Systemic mycoses have been viewed as neglected diseases and they are responsible for deaths and disabilities around the world. Rapid, low-cost, simple, highly-specific and sensitive diagnostic tests are critical components of patient care, disease control and active surveillance. However, the diagnosis of fungal infections represents a great challenge because of the decline in the expertise needed for identifying fungi, and a reduced number of instruments and assays specific to fungal identification. Unfortunately, time of diagnosis is one of the most important risk factors for mortality rates from many of the systemic mycoses. In addition, phenotypic and biochemical identification methods are often time-consuming, which has created an increasing demand for new methods of fungal identification. In this review, we discuss the current context of the diagnosis of the main systemic mycoses and propose alternative approaches for the identification of new targets for fungal pathogens, which can help in the development of new diagnostic tests.

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Section: Approaches Used To Search For New Diagnostic Candidatesmentioning

confidence: 84%

Challenges in Serologic Diagnostics of Neglected Human Systemic Mycoses: An Overview on Characterization of New Targets

et al. 2022

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“… 56 The ligand binds with pockets when they are geometrically compatible with binding site assembly. 57 A binding site score of zero for the Mast-Cs complex indicated that mastoparan binding sites were well encapsulated in the chitosan ring and there was no opportunity to interact with proteases and peptidases. This made the Mast-Cs nanocomplex suitable for in vivo therapeutic evaluation ( Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

Therapeutic Potential of Novel Mastoparan-Chitosan Nanoconstructs Against Clinical MDR Acinetobacter baumannii: In silico, in vitro and in vivo Studies

Hassan

Ikram

Raza

et al. 2021

IJN

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Purpose Acinetobacter baumannii antibiotic resistant infections in high-risk patients are a great challenge for researchers and clinicians worldwide. In an effort to achieve potent bactericidal outcomes, a novel chitosan–mastoparan nanoconstruct (Mast-Cs NC) was designed and assessed for its therapeutic potential through in silico, in vitro and in vivo experimentation against clinical multidrug-resistant (MDR) A. baumannii . Methods Optimized 3D structures of mastoparan and chitosan were coupled computationally through an ionic cross-linker to generate a circular ring of chitosan encasing mastoparan. The complex was assessed for interactions and stability through molecular dynamic simulation (MDS). Binding pocket analysis was used to assess the protease–peptide interface. Mast-Cs NC were prepared by the ionic gelation method. Mast-Cs NC were evaluated in vitro and in vivo for their therapeutic efficacy against drug-resistant clinical A. baumannii . Results MDS for 100 ns showed stable bonds between chitosan and mastoparan; the first at chitosan oxygen atom-46 and mastoparan isoleucine carbon atom with a distance of 2.77 Å, and the second between oxygen atom-23 and mastoparan lysine nitrogen atom with a distance of 2.80 Å, and binding energies of −3.6 and −7.4 kcal/mol, respectively. Mast-Cs complexes approximately 156 nm in size, with +54.9 mV zeta potential and 22.63% loading capacity, offered >90% encapsulation efficiency and were found to be geometrically incompatible with binding pockets of various proteases. The MIC 90 of Mast-Cs NC was significantly lower than that of chitosan (4 vs 512 μg/mL, respectively, p <0.05), with noticeable bacterial damage upon morphological analysis. In a BALB/c mouse sepsis model, a significant reduction in bacterial colony count in the Mast-Cs treated group was observed compared with chitosan and mastoparan alone ( p <0.005). Mast-Cs maintained good biocompatibility and cytocompatibility. Conclusion Novel mastoparan-loaded chitosan nanoconstructs signify a successful strategy for achieving a synergistic bactericidal effect and higher therapeutic efficacy against MDR clinical A. baumannii isolates. The Mast-Cs nano-drug delivery system could work as an alternative promising treatment option against MDR A. baumannii .

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“…Despite the methodological advancements, the high throughput experimental results are yet not available for the majority of pathogens. As a result, the efforts to find essential drug targets now mostly rely on bioinformatics based predictions ( Uddin and Rafi, 2017 ). In silico based subtractive genomic analysis has been widely applied for strain-specific drug target identifications, particularly for the resistant pathogens ( Uddin et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Comparative Metabolic Pathways Analysis and Subtractive Genomics Profiling to Prioritize Potential Drug Targets Against Streptococcus pneumoniae

et al. 2022

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Structural and functional characterization of a unique hypothetical protein (WP_003901628.1) of Mycobacterium tuberculosis: a computational approach

Cited by 9 publications

References 61 publications

Challenges in Serologic Diagnostics of Neglected Human Systemic Mycoses: An Overview on Characterization of New Targets

Challenges in Serologic Diagnostics of Neglected Human Systemic Mycoses: An Overview on Characterization of New Targets

Therapeutic Potential of Novel Mastoparan-Chitosan Nanoconstructs Against Clinical MDR Acinetobacter baumannii: In silico, in vitro and in vivo Studies

Comparative Metabolic Pathways Analysis and Subtractive Genomics Profiling to Prioritize Potential Drug Targets Against Streptococcus pneumoniae

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