In silico investigation by conceptual DFT and molecular docking of antitrypanosomal compounds for understanding cruzain inhibition

Current knowledge about Chagas disease, the potentially life-threatening illness caused by the protozoan parasite (Trypanosoma cruzi), has led to the development of new drugs and the understanding of their mode of action. The Conceptual Density-Functional Theory was applied to determine the active center sites of trypanocidal compounds, extended by the Molecular Docking analysis to identify the most favorable ligand conformation when bound to the active site of cruzain. Results such as CHELPG charges, Fukui function, MESP, and Molecular Docking analysis are reported and discussed in the present investigation. Whereas, a close agreement with experimental results was found to explain the possibility of studying the receptor-binding mode using these different axes.

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Vibrational spectral, density functional theory and molecular docking analysis on 4-nitrobenzohydrazide

Journal of Molecular Structure ◽

10.1016/j.molstruc.2020.128948 ◽

2021 ◽

Vol 1223 ◽

pp. 128948

Author(s):

H. Marshan Robert ◽

D Usha ◽

M. Amalanathan ◽

R. Racil Jeya Geetha ◽

M. Sony Michael Mary

Keyword(s):

Density Functional Theory ◽

Molecular Docking ◽

Spectral Density ◽

Density Functional ◽

Functional Theory ◽

Docking Analysis ◽

Molecular Docking Analysis

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Binding Mode Prediction of 5-Hydroxytryptamine 2C Receptor Ligands by Homology Modeling and Molecular Docking Analysis

Bulletin of the Korean Chemical Society ◽

10.5012/bkcs.2011.32.6.2008 ◽

2011 ◽

Vol 32 (6) ◽

pp. 2008-2014 ◽

Cited By ~ 3

Author(s):

Asif Ahmed ◽

Shanthi Nagarajan ◽

Munikumar Reddy Doddareddy ◽

Yong-Seo Cho ◽

Ae-Nim Pae

Keyword(s):

Molecular Docking ◽

Homology Modeling ◽

Binding Mode ◽

Receptor Ligands ◽

Docking Analysis ◽

Binding Mode Prediction ◽

Molecular Docking Analysis

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Molecular modeling and docking analysis of bis-indolymethanes derivatives as human β-glucuronidase enzyme inhibitors

Bayero Journal of Pure and Applied Sciences ◽

10.4314/bajopas.v14i1.4 ◽

2021 ◽

Vol 14 (1) ◽

pp. 21-30

Author(s):

M.T. Ibrahim ◽

U. Muhammad

Keyword(s):

Molecular Docking ◽

Physicochemical Parameters ◽

Enzyme Inhibitors ◽

Dft Method ◽

Binding Pocket ◽

Binding Mode ◽

Docking Analysis ◽

Molecular Modeling And Docking ◽

Molecular Docking Analysis ◽

Better Than

β-glucuronidase enzyme is present mostly in mammals’ tissues. β-glucuronidase is present in kidney, bile, serum, urine and spleen. In eukaryotic and prokaryotic organisms, it is important in the process of breaking down of β-glucuronide. It also helps in the neutralization of reactivity of some metabolites that are associated to many diseases. The most stable geometry of the dataset were obtained adopting DFT method at B3LYP/6-31G* level of theory. The model was developed using MLR analysis adopting GFA method. Molecular docking was also performed to portray the binding mode of these bis-indolymethanes derivatives in the binding pocket of their target receptor (human β-glucuronidase). The selected model was assessed and chosen based on its statistical fitness with R2trng=0.907233, R2adj=0.881465, Qcv2=0.833795, and R2test=0.609841. And also, the significance and impart of each physicochemical parameters to the selected model were determine by their ME values. Molecular docking analysis revealed that amino acid such as ALA49, SER52, ASP53, PHE51, VAL96, LEU92, TYR188, TYR199 and PHE200 might be responsible for the most promised binding affinity of the reported docked ligands. The molecular docking results showed that the reported compounds were better than the standard β-glucuronidase inhibitor. The results of this findings paved way for designing novel β-lucuronidase inhibitors.

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Analysis of the Molecular Interactions between Cytochromes P450 3A4 and 1A2 and Aflatoxins: A Docking Study

Applied Sciences ◽

10.3390/app9122467 ◽

2019 ◽

Vol 9 (12) ◽

pp. 2467 ◽

Cited By ~ 2

Author(s):

Isui Abril García-Montoya ◽

Norma Rosario Flores-Holguín ◽

Linda-Lucila Landeros-Martínez ◽

Mónica Alvarado-González ◽

Quintín Rascón-Cruz ◽

...

Keyword(s):

Molecular Structure ◽

Amino Acids ◽

Molecular Docking ◽

Charge Transfer ◽

Active Site ◽

Density Functional ◽

Chemical Reactivity ◽

Cytochromes P450 ◽

Docking Analysis ◽

Molecular Docking Analysis

Mycotoxins known as aflatoxins (AF) are produced as a secondary metabolite by some species of Aspergillus fungi. They are considered carcinogenic, hepatotoxic, teratogenic, and mutagenic. In this study, the molecular structure, chemical reactivity, and charge transfer values of AFB1, B2, G1, and G2 were analyzed using density functional theory. Different methodologies—B3LYP/6-311G(d,p) and M06-2X/6-311G(d,p)—were applied for geometrical calculations. Chemical reactivity parameters were used in the calculation of charge transfer values during the interaction between protein and ligand. The binding energy, the electrostatic interactions, and the amino acids of the active site were determined by molecular docking analysis between AF and cytochromes P450 (3A4 and 1A2), employing different PDB files (CYP3A4:1TQN, 2V0M, 4NY4 and 1W0E, and CYP1A2:2HI4). Molecular docking analysis indicated that the central rings of the AF are involved in the interaction with the HEM group of the active site. The differences in the molecular structure of the AF affect their position regarding the HEM group. The resulting configurations presented considerable variation in the amino acids and the position of the coupling. The charge transfer values showed that there is oxidative damage inside the active site and that the HEM group is responsible for the main charge transferences.

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Mechanism of Cordyceps Cicadae in Treating Diabetic Nephropathy Based on Network Pharmacology and Molecular Docking Analysis

Journal of Diabetes Research ◽

10.1155/2021/5477941 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Yi Qian ◽

Xin Sun ◽

Xin Wang ◽

Xin Yang ◽

Mengyao Fan ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Molecular Docking ◽

Docking Studies ◽

New Drugs ◽

Network Pharmacology ◽

Active Components ◽

Docking Analysis ◽

Discovery Studio ◽

Cordyceps Cicadae ◽

Molecular Docking Analysis

Objective. To systematically study the mechanism of cordyceps cicadae in the treatment of diabetic nephropathy (DN) with the method of network pharmacology and molecular docking analysis, so as to provide theoretical basis for the development of new drugs for the treatment of DN. Methods. TCMSP, Symmap, PubChem, PubMed, and CTD database were used to predict and screen the active components and therapeutic targets for DN. The network of active components and targets was drawn by Cytoscape 3.6.0, the protein-protein interaction (PPI) was analyzed by the STRING database, and the DAVID database was used for the enrichment analysis of intersection targets. Molecular docking studies were finished by Discovery Studio 3.5. Results. A total of 36 active compounds, including myriocin, guanosine, and inosine, and 378 potential targets of cordyceps cicadae were obtained. PPI network analysis showed that AKT1, MAPK8, and TP53 and other targets were related to both cordyceps cicadae and DN. GO and KEGG pathway analysis showed that these targets were mostly involved in R-HSA-450341, 157.14-3-3 cell cycle, and PDGF pathways. Docking studies suggested that myriocin can fit in the binding pocket of two target proteins (AKT1 and MAPK8). Conclusion. Active ingredients of cordyceps cicadae such as myriocin may act on DN through different targets such as AKT1, MAPK8, and TP53 and other targets, which can help to develop innovative drugs for effective treatment of DN.

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