Interaction Analysis of T7 RNA Polymerase with Heparin and Its Low Molecular Weight Derivatives – An in Silico Approach

Borkotoky, Subhomoi; Meena, Chetan Kumar; Murali, Ayaluru

doi:10.4137/bbi.s40427

Cited by 42 publications

(26 citation statements)

References 56 publications

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“…As the focus of this study is pH dependence and many of these unaccounted sequences contain titrable residues, we have used the modelled full-length structure of T7RNAP, determined by homology modelling with Mg 2+ ions at the catalytic centre 6 .…”

Section: Methodsmentioning

confidence: 99%

An in-silico glimpse into the pH dependent structural changes of T7 RNA polymerase: a protein with simplicity

Borkotoky

Meena

Bhalerao

et al. 2017

Sci Rep

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The capability of performing an array of functions with its single subunit structure makes T7 RNA polymerase (T7RNAP) as one of the simplest yet attractive target for various investigations ranging from structure determinations to several biological tests. In this study, with the help of molecular dynamics (MD) calculations and molecular docking, we investigated the effect of varying pH conditions on conformational flexibility of T7RNAP. We also studied its effect on the interactions with a well established inhibitor (heparin), substrate GTP and T7 promoter of T7RNAP. The simulation studies were validated with the help of three dimensional reconstructions of the polymerase at different pH environments using transmission electron microscopy and single particle analysis. On comparing the simulated structures, it was observed that the structure of T7RNAP changes considerably and interactions with its binding partners also changes as the pH shifts from basic to acidic. Further, it was observed that the C-terminal end plays a vital role in the inefficiency of the polymerase at low pH. Thus, this in-silico study may provide a significant insight into the structural investigations on T7RNAP as well as in designing potent inhibitors against it in varying pH environments.

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Section: Methodsmentioning

confidence: 99%

An in-silico glimpse into the pH dependent structural changes of T7 RNA polymerase: a protein with simplicity

Borkotoky

Meena

Bhalerao

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

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Section: Prime Mm-gbsa Calculationmentioning

confidence: 99%

“…Molecular mechanics-generalized Born surface area (MM-GBSA) method was used as a post-docking validation tool [63] . The binding energy calculated by MM-GBSA shows a reasonably good correlation between the predicted and the experimental binding affinity [63] . Besides, the post-docking binding energy calculation is more efficient when the ranking of congeneric inhibitors is emphasized [64,65] .…”

Section: Prime Mm-gbsa Calculationmentioning

confidence: 99%

“…The molecular dynamics simulation (MDS) is essential to evaluate the stability of the receptor-ligand complex [70] and to understand how they would behave in a pre-defined environment through atomic movements [63] . Therefore, we performed the MDS of the two most promising ligand-receptor complexes using YASARA Dynamics with AMBER14 force field [71,72] .…”

Section: Molecular Dynamic Simulationmentioning

confidence: 99%

“…Molecular dynamics simulation (MDS) is essential to determine the stability of the receptor-ligand complex [63] . MD simulation study for 30 ns time span provides insights into stable molecular interactions between docked protein-ligand complexes under specific physiological circumstances.…”

Section: Dynamic Simulation Studiesmentioning

confidence: 99%

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Energy-Optimized Pharmacophore Coupled Virtual Screening in the Discovery of Quorum Sensing Inhibitors of LasR Protein of <em>Pseudomonas aeruginosa</em>

Nain¹,

Syed²,

Karim³

et al. 2019

Preprint

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Pseudomonas aeruginosa is an emerging opportunistic pathogen responsible for cystic fibrosis and nosocomial infections. In addition, empirical treatments are become inefficient due to their multiple-antibiotic resistance and extensive colonizing ability. Quorum sensing (QS) plays a vital role in the regulation of virulence factors in P. aeruginosa. Attenuation of virulence by QS inhibition could be an alternative and effective approach to control infections. Therefore, we sought to discover new QS inhibitors (QSIs) against LasR receptor in P. aeruginosa using chemoinformatics. Initially, a structure-based high-throughput virtual screening was performed using the LasR active site that identified 61404 relevant molecules. E-pharmacophore (ADAHH) screening of these molecules rendered 72 QSI candidates. In standard-precision docking, only 7 compounds were found as potential QSIs due to their higher binding affinity to LasR receptor (-7.53 to -10.32 kcal/mol compared to -7.43 kcal/mol of native ligands). The ADMET properties of these compounds were suitable to be QSIs. Later, extra-precision docking and binding energy calculation suggested ZINC19765885 and ZINC72387263 as the most promising QSIs. The dynamic simulation of the docked complexes showed good binding stability and molecular interactions. The current study suggested that these two compounds could be used in P. aeruginosa QS inhibition to combat bacterial infections.

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The inhibitory potential of chemical constituents of Ficus carica targeting interleukin‐6 (IL‐6) mediated inflammation

Mansoor

Ahmed

Rasool

2023

Cell Biochemistry & Function

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Inflammation is an innate reaction of the body of an individual when subjected to the noxious factors repeatedly. Pharmacological approaches focused at disrupting cytokine signaling networks have become significant therapeutic alternatives for the treatment of inflammatory illnesses, cancer and autoimmune disorders. High levels of inflammatory mediators, particularly interleukin IL‐1, IL‐6, IL‐18, IL‐12, and tumor necrosis factor alpha leads to a cytokine storm in the body. Among all the released cytokines in a patient suffering from inflammatory disorder, IL‐6 mediator has a pivotal role in this inflammatory cascade which progresses to a cytokine storm. Therefore, the blockage of the IL‐6 inflammatory mediator could be a promising treatment option for the patients with hyper inflammatory conditions. The phytochemicals could provide the new lead compounds against the IL‐6 mediator. Ficus carica has been the ideal plant of research and investigation due to its commercial, economic and medical importance. The anti‐inflammatory properties of F. carica were further investigated by in silico and in vivo approaches. The docking scores of Cyanidin‐3,5‐diglucoside, Kaempferol‐7‐O‐rutinoside, Cyanidin‐3‐rhamnoglucoside, and Rutin are −9.231, −8.921, −8.840, and −8.335 Kcal/mole respectively. The free energy of binding and stability of the docked complexes of these top four phytochemicals with the IL‐6 were further analyzed by Molecular Mechanics‐Generalized Born Surface Area and Molecular Dynamic simulations, respectively. The in vivo anti‐inflammatory carrageenan‐induced rat paw edema model was used for the validation of in silico results. The maximum percentage paw edema inhibition with petroleum ether and ethyl acetate was 70.32% and 45.05%, respectively. The in vivo anti‐inflammatory activity confirms the anti‐inflammatory potential of F. carica. Therefore, it is predicted that Cyanidin‐3,5‐diglucoside, Kaempferol‐7‐O‐rutinoside, Cyanidin‐3‐rhamnoglucoside, and Rutin have the potential to inhibit the IL‐6 mediator which will aid in mitigating the cytokine storm in patients with acute inflammations.

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Interaction Analysis of T7 RNA Polymerase with Heparin and Its Low Molecular Weight Derivatives – An in Silico Approach

Cited by 42 publications

References 56 publications

An in-silico glimpse into the pH dependent structural changes of T7 RNA polymerase: a protein with simplicity

An in-silico glimpse into the pH dependent structural changes of T7 RNA polymerase: a protein with simplicity

Energy-Optimized Pharmacophore Coupled Virtual Screening in the Discovery of Quorum Sensing Inhibitors of LasR Protein of <em>Pseudomonas aeruginosa</em>

The inhibitory potential of chemical constituents of Ficus carica targeting interleukin‐6 (IL‐6) mediated inflammation

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