In-silico functional and structural annotation of hypothetical protein from Klebsiella pneumonia: A potential drug target

Singh, Vishal; Dhankhar, Poonam; Dalal, Vikram; Tomar, Shailly; Kumar, Pravindra

doi:10.1016/j.jmgm.2022.108262

Cited by 30 publications

(21 citation statements)

References 70 publications

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“…Virulence factor database (VFDB) (http://www.mgc.ac.cn/VFs/) revealed no similarity of FmtA with the S. aureus virulence factors. 49,58 Gemifloxacin, paromomycin, tobramycin and streptomycin are aminoglycoside antibacterial agents which are known to treat a wide variety of bacterial infections. 59−63 Gemifloxacin functions by preventing DNA synthesis by hampering both DNA gyrase and topoisomerase IV, which are crucial for microbial life cycle.…”

Section: Discussionmentioning

confidence: 99%

“…Virulence factor database (VFDB) () revealed no similarity of FmtA with the S. aureus virulence factors. , …”

Section: Discussionmentioning

confidence: 99%

“…The molecular mechanics Poisson–Boltzmann surface area (MMPBSA) method was utilized to determine the binding affinity of FmtA–drug(s) complexes. − Here, a total of 2000 snapshots from the last 20 ns of molecular dynamics were utilized to calculate the binding energy of FmtA–gemifloxacin, FmtA–paromomycin, FmtA–streptomycin, and FmtA–tobramycin complexes . The per residue decomposition analysis was performed to calculate the binding energy contribution of active site residues with the ligand in FmtA–drug(s) complexes. , …”

Section: Methodsmentioning

confidence: 99%

“…48 The per residue decomposition analysis was performed to calculate the binding energy contribution of active site residues with the ligand in FmtA−drug(s) complexes. 49,50 2.4. Quantum Mechanics and Quantum Mechanics/ Molecular Mechanics.…”

Section: Virtual Screening and Molecular Dockingmentioning

confidence: 99%

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Drug-Repurposing Approach To Combat Staphylococcus aureus: Biomolecular and Binding Interaction Study

et al. 2022

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Staphylococcus aureus is considered as one of the most widespread bacterial pathogens and continues to be a prevalent cause of mortality and morbidity across the globe. FmtA is a key factor linked with methicillin resistance in S. aureus. Consequently, new antibacterial compounds are crucial to combat S. aureus resistance. Here, we present the virtual screening of a set of compounds against the available crystal structure of FmtA. The findings indicate that gemifloxacin, paromomycin, streptomycin, and tobramycin were the top-ranked potential drug molecules based on the binding affinity. Furthermore, these drug molecules were analyzed with molecular dynamics simulations, which showed that the identified molecules formed highly stable FmtA–inhibitor(s) complexes. Molecular mechanics Poisson–Boltzmann surface area and quantum mechanics/molecular mechanics calculations suggested that the active site residues (Ser127, Lys130, Tyr211, and Asp213) of FmtA are crucial for the interaction with the inhibitor(s) to form stable protein–inhibitor(s) complexes. Moreover, fluorescence- and isothermal calorimetry-based binding studies showed that all the molecules possess dissociation constant values in the micromolar scale, revealing a strong binding affinity with FmtAΔ80, leading to stable protein–drug(s) complexes. The findings of this study present potential beginning points for the rational development of advanced, safe, and efficacious antibacterial agents targeting FmtA.

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Section: Discussionmentioning

confidence: 99%

“…Virulence factor database (VFDB) () revealed no similarity of FmtA with the S. aureus virulence factors. , …”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Virtual Screening and Molecular Dockingmentioning

confidence: 99%

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Drug-Repurposing Approach To Combat Staphylococcus aureus: Biomolecular and Binding Interaction Study

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“…The visualization was done to analyse the interaction between ligands and residues of amino acid residues on each protein by PyMOL software. The binding energy calculation (MM-GBSA) was further conducted using Prime in Maestro to analyse the potential biological response of the free binding energy of the ligands that are binding to the active site of the protein in the docked complex, using XP docking mode [ 40 , 41 , 42 ].…”

Section: Methodsmentioning

confidence: 99%

Molecular Docking of Bacterial Protein Modulators and Pharmacotherapeutics of Carica papaya Leaves as a Promising Therapy for Sepsis: Synchronising In Silico and In Vitro Studies

et al. 2023

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Sepsis is a serious health concern globally, which necessitates understanding the root cause of infection for the prevention of proliferation inside the host’s body. Phytochemicals present in plants exhibit antibacterial and anti-proliferative properties stipulated for sepsis treatment. The aim of the study was to determine the potential role of Carica papaya leaf extract for sepsis treatment in silico and in vitro. We selected two phytochemical compounds, carpaine and quercetin, and docked them with bacterial proteins, heat shock protein (PDB ID: 4PO2), surfactant protein D (PDB ID: 1PW9), and lactobacillus bacterial protein (PDB ID: 4MKS) against imipenem and cyclophosphamide. Quercetin showed the strongest interaction with 1PW9 and 4MKS proteins. The leaves were extracted using ethanol, methanol, and water through Soxhlet extraction. Total flavonoid content, DPPH assay, HPTLC, and FTIR were performed. In vitro cytotoxicity of ethanol extract was screened via MTT assay on the J774 cell line. Ethanol extract (EE) possessed the maximum number of phytocomponents, the highest amount of flavonoid content, and the maximum antioxidant activity compared to other extracts. FTIR analysis confirmed the presence of N-H, O-H, C-H, C=O, C=C, and C-Cl functional groups in ethanol extract. Cell viability was highest (100%) at 25 µg/mL of EE. The present study demonstrated that the papaya leaves possessed antibacterial and cytotoxic activity against sepsis infection.

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Antipsychotics Induced Reproductive Toxicity by Stimulating Oxidative Stress: A Comparative in Vivo and in Silico Study

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et al. 2023

Chemistry & Biodiversity

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The pathophysiological mechanism behind the link between antipsychotic drugs and sexual dysfunction is still unknown. The goal of this research is to compare the potential effects of antipsychotics on the male reproductive system. Fifty rats were randomly assigned into the five groups indicated: Control, Haloperidol, Risperidone, Quetiapine and Aripiprazole. Sperm parameters were significantly impaired in all antipsychoticstreated groups. Haloperidol and Risperidone significantly decreased the level of testosterone. All antipsychotics had significantly reduced inhibin B level. A significant reduction was observed in SOD activity in all antipsychotics-treated groups. While GSH levels diminished, MDA levels were rising in the Haloperidol and Risperidone groups. Also, the GSH level was significantly elevated in the Quetiapine and Aripiprazole groups. By causing oxidative stress and altering hormone levels, Haloperidol and Risperidone are damaging to male reproductivity. This study represents useful starting point for exploring further aspects of the underlying mechanisms reproductive toxicity of antipsychotics.

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In-silico functional and structural annotation of hypothetical protein from Klebsiella pneumonia: A potential drug target

Cited by 30 publications

References 70 publications

Drug-Repurposing Approach To Combat Staphylococcus aureus: Biomolecular and Binding Interaction Study

Drug-Repurposing Approach To Combat Staphylococcus aureus: Biomolecular and Binding Interaction Study

Molecular Docking of Bacterial Protein Modulators and Pharmacotherapeutics of Carica papaya Leaves as a Promising Therapy for Sepsis: Synchronising In Silico and In Vitro Studies

Antipsychotics Induced Reproductive Toxicity by Stimulating Oxidative Stress: A Comparative in Vivo and in Silico Study

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