MurC ligase of multi-drug resistant Salmonella Typhi can be inhibited by novel Curcumin derivative: Evidence from molecular docking and dynamics simulations

Debroy, Reetika; Ramaiah, Sudha

doi:10.1016/j.biocel.2022.106279

Cited by 22 publications

(15 citation statements)

References 28 publications

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“…1 b). The cluster further highlighted macB , acrA and acrB as highly interacting genes, which have also been previously proposed as therapeutic targets against AMR-linked bacterial infections (Miryala et al 2021a ; Debroy and Ramaiah 2022 ). Furthermore, experimental reports have implied resistance patterns by acrA,B towards β-lactams and CAMP molecules in Salmonella typhimurium and E. coli respectively (Nikaido et al 1998 ), thus correlating with the FEA of acrA,B from the current study (ecln01501; ecln01503).…”

Section: Discussionmentioning

confidence: 75%

“…Protein−ligand docked poses and their intermolecular interactions were visualized in Discovery Studio Visualizer v2020. Moreover, comparative molecular docking of the drug-target with a standard antibiotic (with reported inhibition profile against the drug-target) was further performed to provide a quantitative measure of docking efficacy between the novel lead and the protein (Debroy and Ramaiah 2022 ).…”

Section: Methodsmentioning

confidence: 99%

“…Gene Interaction Network (GIN) approach integrated with structural bioinformatics can be useful in understanding the complex molecular interactions among the biomolecules present in the physiological systems (Naha et al 2022 ; Priyamvada et al 2022 ; Ashok and Ramaiah 2022 ). Our research group has previously decoded complex metabolic pathways and identified potent drug targets using network biology studies (Ashok et al 2021 , 2022 ; Naha and Ramaiah 2022 ), as well as integrated structural bioinformatics to predict effective lead molecules to circumvent several infectious and systemic diseases (Vasudevan et al 2021 ; Miryala et al 2021b ; Debroy and Ramaiah 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Translational protein RpsE as an alternative target for novel nucleoside analogues to treat MDR Enterobacter cloacae ATCC 13047: network analysis and molecular dynamics study

Debroy

Ramaiah

2023

World J Microbiol Biotechnol

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The pathogenic Enterobacter cloacae subsp. cloacae str. ATCC 13047 has contemporarily emerged as a multi-drug resistant strain. To formulate an effective treatment option, alternative therapeutic methods need to be explored. The present study focused on Gene Interaction Network study of 46 antimicrobial resistance genes to reveal the densely interconnecting and functional hub genes in E. cloacae ATCC 13047. The AMR genes were subjected to clustering, topological and functional enrichment analysis, revealing rpsE (RpsE), acrA (AcrA) and arnT (ArnT) as novel therapeutic drug targets for hindering drug resistance in the pathogenic strain. Network topology further indicated translational protein RpsE to be exploited as a promising drug-target candidate for which the structure was predicted, optimized and validated through molecular dynamics simulations (MDS). Absorption, distribution, metabolism and excretion screening recognized ZINC5441082 ( N -Isopentyladenosine) (Lead_1) and ZINC1319816 (cyclopentyl-aminopurinyl-hydroxymethyl-oxolanediol) (Lead_2) as orally bioavailable compounds against RpsE. Molecular docking and MDS confirmed the binding efficacy and protein−ligand complex stability. Furthermore, binding free energy (G bind ) calculations, principal component and free energy landscape analyses affirmed the predicted nucleoside analogues against RpsE protein to be comprehensively examined as a potential treatment strategy against E. cloacae ATCC 13047. Supplementary information The online version contains supplementary material available at 10.1007/s11274-023-03634-z.

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Section: Discussionmentioning

confidence: 75%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Translational protein RpsE as an alternative target for novel nucleoside analogues to treat MDR Enterobacter cloacae ATCC 13047: network analysis and molecular dynamics study

Debroy

Ramaiah

2023

World J Microbiol Biotechnol

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“…A pharmacophore map evaluates the chemical properties of a compound based on its interactions with receptors 13 . Phase is a robust pharmacophore module in the Schrödinger 2020.1 suite, and it is a multipurpose tool for pharmacophore perception, alignment, and prediction of activity within 3D databases 14 .…”

Section: Methodsmentioning

confidence: 99%

“…A pharmacophore map evaluates the chemical properties of a compound based on its interactions with receptors. 13 Phase is a robust pharmacophore module in the Schrödinger 2020.1 suite, and it is a multipurpose tool for pharmacophore perception, alignment, and prediction of activity within 3D databases. 14 A common pharmacophore model with three known NURR1 inducers (Chloroquine, Amodiaquine, and Glafenine) was constructed using six standard pharmacophore features such as hydrogen bond donor (D), hydrogen bond acceptor (A), hydrophobic group (H), positive and negative ionizable (P, N), and aromatic rings (R).…”

Section: Pharmacophore Mapping and Screening For Nurr1 Inducersmentioning

confidence: 99%

Mechanistic insights into the role of vitamin D and computational identification of potential lead compounds for Parkinson's disease

Marshal

Kuriakose

Alhazmi

et al. 2023

J of Cellular Biochemistry

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Parkinson's disease (PD) is the second most common neurodegenerative disorder that affects dopaminergic neurons in the midbrain. A recent study suggests that Orphan Nuclear Receptor 1 (NURR1) impairment may contribute to PD pathogenesis. Our study found three potent agonists for NURR1 protein based on structural and ligand-based screening methods. The pharmacophore is comprised of a hydrogen bond donor, a hydrophobic group, and two aromatic rings (DHRR). The Pharmacophore screening method screened 3142 compounds, of which 3 were screened using structure-based screening. An analysis of the molecules using Molecular Mechanics-Generalized Born Surface Area (binding free energy) revealed a range of −46.77 to −59.06 Kcal/mol. After that, chemical reactivity was investigated by density functional theory, and molecular dynamics simulation was performed (protein-ligand stability). Based on the computational studies, Lifechemical_16901310, Maybridge_2815310, and NPACT_392450 are promising agonists with respect to NURR1. To confirm the potency of the identified compounds, further validation and experiments must be conducted.

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FN1 and cancer‐associated fibroblasts markers influence immune microenvironment in clear cell renal cell carcinoma

Ashok

Ramaiah

2023

The Journal of Gene Medicine

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BackgroundAltered tumor microenvironment (TME) is characterized in clear cell renal cell carcinoma (ccRCC) as a result of the heterogeneity observed in the TME. Modulations in TME have shown tumor metastasis promotion; hence, identifying TME‐based biomarkers can be critical for theranostics application.MethodsHere, we performed an integrated systems biology approach utilizing differential gene expression, network metrics and clinical samples cohorts to prioritize the major deregulated genes and their associated pathways specific for metastasis.ResultsThe gene expression profiling of 140 ccRCC samples resulted in 3657 differentially expressed genes, from which a network of 1867 up‐regulated genes were further computed using network metrics for screening hub‐genes. The specific pathways of ccRCC entailed through functional enrichment analysis of the hub‐gene clusters indicated the role of the identified hub‐genes in the enriched pathways, further validating the functional significance of the hub‐genes. The positive correlation of TME cells, namely cancer‐associated fibroblasts (CAFs) and its biomarkers (FAP and S100A4) with FN1, signified the role of hub‐gene signaling for promoting metastasis in ccRCC. Thereafter, comparative expression, differential methylation, genetic alteration and overall survival analysis were analyzed to validate the screened hub‐genes.ConclusionsThe hub‐genes were validated and prioritized by correlating with expression‐based parameters, including histological grades, tumor, metastatic and pathological stages (based on median transcript per million; analysis of variance [ANOVA], P ≤ 0.05) from a clinically curated ccRCC dataset to further substantiate the translational benefits of the screened hub‐genes as potential diagnostic biomarkers for ccRCC.

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MurC ligase of multi-drug resistant Salmonella Typhi can be inhibited by novel Curcumin derivative: Evidence from molecular docking and dynamics simulations

Cited by 22 publications

References 28 publications

Translational protein RpsE as an alternative target for novel nucleoside analogues to treat MDR Enterobacter cloacae ATCC 13047: network analysis and molecular dynamics study

Translational protein RpsE as an alternative target for novel nucleoside analogues to treat MDR Enterobacter cloacae ATCC 13047: network analysis and molecular dynamics study

Mechanistic insights into the role of vitamin D and computational identification of potential lead compounds for Parkinson's disease

FN1 and cancer‐associated fibroblasts markers influence immune microenvironment in clear cell renal cell carcinoma

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