Identification of potential inhibitors for LLM of<i>Staphylococcus aureus</i>: structure-based pharmacophore modeling, molecular dynamics, and binding free energy studies

Kumari, Reena; Dalal, Vikram

doi:10.1080/07391102.2021.1936179

Cited by 37 publications

(20 citation statements)

References 70 publications

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“…By monitoring the RMSD during the molecular simulation, the dynamics variation in Cα backbone of the complexes was detected ( Kumari and Dalal, 2021 ). Based on the RMSD plot ( Figure 6 ), all the three complexes attained stability after 50 ns till 200 ns.…”

Section: Resultsmentioning

confidence: 99%

“…RMSF analysis shows the flexibility and fluctuations of the protein in complex compared to the native protein. The higher RMSF values indicate that there are loosely organized loops and turns, while lower flexibility shows the secondary structures like helixes and sheets ( Kumari and Dalal, 2021 ). The RMSF plot ( Supplementary Figure S3 ) showed that most of the residues in native protein had higher fluctuations than those in the complexes, showing that binding of ligands had decreased the fluctuations in the protein, were well-fitted, and formed a stable complex.…”

Section: Resultsmentioning

confidence: 99%

“…The polar and non-polar interactions of the protein determine its surface area, which is known as the Solvent Accessible Surface Area (SASA). SASA of a protein decreases when there is an increase in compactness of a protein ( Kumari and Dalal, 2021 ). The SASA plot ( Supplementary Figure S5 ) showed that, after 100 ns, the complexes had slightly higher values than the native protein.…”

Section: Resultsmentioning

confidence: 99%

“…The Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) approach was utilized to evaluate the binding free energies of all the three natural compounds with Domain 3 of Orf1ab to determine complex stability ( Kumari and Dalal, 2021 ). The gmx_MMPBSA ( Valdés-Tresanco et al, 2021 ) is a tool based on AMBER’s MMPBSA.py which is used to perform binding free energy calculations using AMBERTOOLS ( Case et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

“…The radius of gyration (Rg) analysis shows the overall compactness of the protein during the simulation. Rg demonstrates the moment of inertia of the atoms in the protein from their center of mass during a particular time interval (Kumari and Dalal, 2021). The Rg plot Frontiers in Genetics frontiersin.org (Supplementary Figure S4) showed that, initially, the Rg of all the complexes and native protein was in the range of 2-2.2 nm.…”

Section: Radius Of Gyrationmentioning

confidence: 99%

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In silico prediction of the animal susceptibility and virtual screening of natural compounds against SARS-CoV-2: Molecular dynamics simulation based analysis

et al. 2022

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COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. It has six open reading frames (orf1ab, orf3a, orf6, orf7a, orf8, and orf10), a spike protein, a membrane protein, an envelope small membrane protein, and a nucleocapsid protein, out of which, orf1ab is the largest ORF coding different important non-structural proteins. In this study, an effort was made to evaluate the susceptibility of different animals against SARS-CoV-2 by analyzing the interactions of Spike and ACE2 proteins of the animals and propose a list of potential natural compounds binding to orf1ab of SARS-CoV-2. Here, we analyzed structural interactions between spike proteins of SARS-CoV-2 and the ACE2 receptor of 16 different hosts. A simulation for 50 ns was performed on these complexes. Based on post-simulation analysis, Chelonia mydas was found to have a more stable complex, while Bubalus bubalis, Aquila chrysaetos chrysaetos, Crocodylus porosus, and Loxodonta africana were found to have the least stable complexes with more fluctuations than all other organisms. Apart from that, we performed domain assignment of orf1ab of SARS-CoV-2 and identified 14 distinct domains. Out of these, Domain 3 (DNA/RNA polymerases) was selected as a target, as it showed no similarities with host proteomes and was validated in silico. Then, the top 10 molecules were selected from the virtual screening of ∼1.8 lakh molecules from the ZINC database, based on binding energy, and validated for ADME and toxicological properties. Three molecules were selected and analyzed further. The structural analysis showed that these molecules were residing within the pocket of the receptor. Finally, a simulation for 200 ns was performed on complexes with three selected molecules. Based on post-simulation analysis (RMSD, RMSF, Rg, SASA, and energies), the molecule ZINC000103666966 was found as the most suitable inhibitory compound against Domain 3. As this is an in silico prediction, further experimental studies could unravel the potential of the proposed molecule against SARS-CoV-2.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Radius Of Gyrationmentioning

confidence: 99%

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In silico prediction of the animal susceptibility and virtual screening of natural compounds against SARS-CoV-2: Molecular dynamics simulation based analysis

et al. 2022

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Novel Isoxazolylpyrimidine Derivatives: Design, Synthesis, Antifungal Activity and In‐Silico Studies

Nagaraja rao,

Poojary,

Mohan Kumar

et al. 2024

Asian J Org Chem

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The advancement of environmentally friendly chemical synthesis in both academic and corporate research has recently taken on enormous relevance. Pesticides are substances, either chemical or biological, that are used to get rid of or lessen the impact of pests. To control the fungi in crops a new set of isoxazolylpyrimidine derivatives were planned, synthesized, and characterized. The compounds indicated were synthesized in high yields, and their structures were determined using elemental analysis, 1H‐NMR, 13C NMR, and LCMS. HPLC was used to assess the purity of the synthesized molecules, and the purity of some compounds were found to be >98% a/a while a couple were found to be >95% a/a. The synthesized compounds were assessed for their antifungal activity. Among these, compounds 5d, 5h, and 5l exhibit substantial antifungal action and considerably suppress the growth of Rhizoctonia solani, Sclerotium rolfsii, and Macrophominaphaseolina. The plausible mechanism of fungal inhibitory activities of rationally designed isoxazolyl pyrimidine derivatives is attributed to the blocking of the oxygen activation of heme Iron in membrane‐bound 14 alpha‐demethylase. The presence of pyrimidine unit in designed materials is a vital factor for inducing antifungal activities, which was further corroborated through the density functional theory (DFT) and molecular docking studies.

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

Dinçer

Yazıcı

Çınar

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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Identification of potential inhibitors for LLM ofStaphylococcus aureus: structure-based pharmacophore modeling, molecular dynamics, and binding free energy studies

Cited by 37 publications

References 70 publications

In silico prediction of the animal susceptibility and virtual screening of natural compounds against SARS-CoV-2: Molecular dynamics simulation based analysis

In silico prediction of the animal susceptibility and virtual screening of natural compounds against SARS-CoV-2: Molecular dynamics simulation based analysis

Novel Isoxazolylpyrimidine Derivatives: Design, Synthesis, Antifungal Activity and In‐Silico Studies

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

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