A molecular docking and dynamic approach to screen inhibitors against ZnuA1 of<i>Candidatus</i>Liberibacter asiaticus

Saini, Gunjan; Dalal, Vikram; Gupta, Deena Nath; Sharma, Nidhi; Kumar, Pravindra; Sharma, Ashwani

doi:10.1080/08927022.2021.1888948

Cited by 18 publications

(7 citation statements)

References 77 publications

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“…It addresses a sequence of databases related to biomedicine and biotechnology and a significant source for bioinformatics tools and services. For the structure identification, SWISS-MODEL and Phyre2 servers were used which presented only 17.21% of the total predicted structure ( Supplementary Figure S1, S2 ) (template: 6G9X) ( Schwede et al, 2003 ; Kelley et al, 2015 ; Saini et al, 2021 ). Therefore, the I-TASSER (Iterative Threading Assembly Refinement) server was used to predict the entire structure of the Rv1250 protein.…”

Section: Methodsmentioning

confidence: 99%

“…Additionally, the model was validated by using ProSA integrated webserver ( https://prosa.services.came.sbg.ac . at/prosa.php) to approximate deviation of Z-score from the high-resolution structures and to determine the error ( Wiederstein and Sippl, 2007 ; Saini et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

“…MD simulation is most widely used to evaluate the stability and to enhance low quality models ( Sokkar et al, 2011 ). Here, it was used to observe the stability of a modelled structure, as well as the stable and static interaction between the ligand and the protein ( Kesari et al, 2020 ; Singh et al, 2020 ; Saini et al, 2021 ; Kumari et al, 2022 ). For MD simulation, firstly GROMACS (Groningen Machine for Chemical Simulations) was used with the GROMOS96 43a1 force field for generating the topology and protein coordinates ( Tran et al, 1996 ; Van Der Spoel et al, 2005 ).…”

Section: Methodsmentioning

confidence: 99%

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Molecular modeling, simulation and docking of Rv1250 protein from Mycobacterium tuberculosis

et al. 2023

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Computational prediction and protein structure modeling have come to the aid of various biological problems in determining the structure of proteins. These technologies have revolutionized the biological world of research, allowing scientists and researchers to gain insights into their biological questions and design experimental research much more efficiently. Pathogenic Mycobacterium spp. is known to stay alive within the macrophages of its host. Mycobacterium tuberculosis is an acid-fast bacterium that is the most common cause of tuberculosis and is considered to be the main cause of resistance of tuberculosis as a leading health issue. The genome of Mycobacterium tuberculosis contains more than 4,000 genes, of which the majority are of unknown function. An attempt has been made to computationally model and dock one of its proteins, Rv1250 (MTV006.22), which is considered as an apparent drug-transporter, integral membrane protein, and member of major facilitator superfamily (MFS). The most widely used techniques, i.e., homology modeling, molecular docking, and molecular dynamics (MD) simulation in the field of structural bioinformatics, have been used in the present work to study the behavior of Rv1250 protein from M. tuberculosis. The structure of unknown TB protein, i.e., Rv1250 was retrived using homology modeling with the help of I-TASSER server. Further, one of the sites responsible for infection was identified and docking was done by using the specific Isoniazid ligand which is an inhibitor of this protein. Finally, the stability of protein model and analysis of stable and static interaction between protein and ligand molecular dynamic simulation was performed at 100 ns The designing of novel Rv1250 enzyme inhibitors is likely achievable with the use of proposed predicted model, which could be helpful in preventing the pathogenesis caused by M. tuberculosis. Finally, the MD simulation was done to evaluate the stability of the ligand for the specific protein.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Molecular modeling, simulation and docking of Rv1250 protein from Mycobacterium tuberculosis

et al. 2023

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“…The 2-dimensional SDF files of these ligands were obtained on Pharmit and converted into 3D formats using the OpenBabel module of the python-based open-source tool, PyRx. 18 For docking purposes, the tool was used to establish a magnetic force field around each of the 691 compounds and the reference, 7,8-DHF, and to minimise the total energy while preserving the intact molecular structure for ligand-receptor interaction. Subsequently, all ligands were converted into their corresponding pdbqt formats.…”

Section: Methodsmentioning

confidence: 99%

Pharmacophore-Aided Virtual Screening and Molecular Dynamics Simulation Identifies TrkB Agonists for Treatment of CDKL5-Deficiency Disorders

Ademuwagun

Oduselu

Rotimi

et al. 2023

Bioinform Biol Insights

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Therapeutic intervention in cyclin-dependent kinase-like 5 (CDKL5) deficiency disorders (CDDs) has remained a concern over the years. Recent advances into the mechanistic interplay of signalling pathways has revealed the role of deficient tropomyosin receptor kinase B (TrkB)/phospholipase C γ1 signalling cascade in CDD. Novel findings showed that in vivo administration of a TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), resulted in a remarkable reversal in the molecular pathologic mechanisms underlying CDD. Owing to this discovery, this study aimed to identify more potent TrkB agonists than 7,8-DHF that could serve as alternatives or combinatorial drugs towards effective management of CDD. Using pharmacophore modelling and multiple database screening, we identified 691 compounds with identical pharmacophore features with 7,8-DHF. Virtual screening of these ligands resulted in identification of at least 6 compounds with better binding affinities than 7,8-DHF. The in silico pharmacokinetic and ADMET studies of the compounds also indicated better drug-like qualities than those of 7,8-DHF. Postdocking analyses and molecular dynamics simulations of the best hits, 6-hydroxy-10-(2-oxo-1-azatricyclo[7.3.1.05,13]trideca-3,5(13),6,8-tetraen-3-yl)-8-oxa-13,14,16-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1,3,6,9,11,15-hexaen-5-one (PubChem: 91637738) and 6-hydroxy-10-(8-methyl-2-oxo-1H-quinolin-3-yl)-8-oxa-13,14,16-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1,3,6,9,11,15-hexaen-5-one (PubChem ID: 91641310), revealed unique ligand interactions, validating the docking findings. We hereby recommend experimental validation of the best hits in CDKL5 knock out models before consideration as drugs in CDD management.

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“…DFT calculation was done to evaluate the polarity of drugs (gemifloxacin, paromomycin, streptomycin, and tobramycin) . The molecular electrostatic potential and molecular orbital energies were assessed by using B3LYP with the basis set of 6-311G (d,p), as done by Dalal et al ,,,, Furthermore, quantum mechanics/molecular mechanics (QM/MM) estimations for FmtA–drug(s) complexes were conducted using our own N-layered integrated molecular orbital and molecular mechanics (ONIOM) method, as done by Dalal et al ,,, The inhibitor and side chain atoms of Ser127, Lys130, Tyr211, and Asp213 were considered in the QM layer, whereas the remaining part of the protein was put in the MM layer. The enthalpy (Δ H ), relative Gibbs free energy (Δ G ), and entropy (Δ S ) were assessed by ONIOM (B3LYP/6-311G(d,p): AMBER).…”

Section: Methodsmentioning

confidence: 99%

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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A molecular docking and dynamic approach to screen inhibitors against ZnuA1 ofCandidatusLiberibacter asiaticus

Cited by 18 publications

References 77 publications

Molecular modeling, simulation and docking of Rv1250 protein from Mycobacterium tuberculosis

Molecular modeling, simulation and docking of Rv1250 protein from Mycobacterium tuberculosis

Pharmacophore-Aided Virtual Screening and Molecular Dynamics Simulation Identifies TrkB Agonists for Treatment of CDKL5-Deficiency Disorders

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

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