Research Outputs
A computational study of the antioxidant power of eugenol compared to Vitamin C
The antioxidant power of eugenol and vitamin C was examined by analyzing the ability of these ligands to bind to the NADPH oxidase protein target and evaluating their bond interactions with critical residues. The results confirm that docked ligands are more stable in the specified active region of 2CDU during a MD simulation of 100 ns and 2CDU protein-ligand interactions with docked ligands showed significant hydrogen bond, hydrophobic, and water bridge formation. Eugenol exhibits hydrogen bond interactions with critical residues in the selective pocket in comparison to vitamin C. Also, eugenol had a similar binding orientation and very considerable stability in the selective pocket of 2CDU with a high binding energy with lipophilic energy. The electrostatic potential maps indicate that for eugenol, the –OH and –OCH3 sites, while that the –OH and –CO functional groups in vitamin C are responsible of the antioxidant activities of these compounds. HAT and SET mechanisms suggest that eugenol may become a better antioxidant than vitamin C.
A computational study of steviol and its suggested anticancer activity. A DFT and docking study
In the present, study we analyzed the electronic properties of Steviol, the Stevia rebaudiana metabolite, and its interaction with antiapoptotic protein BCL-2. The ionization potential and electrophilicity index values were evaluated in the framework of the DFT, and these values suggest that Steviol may form ligand-receptor interactions. Also, the bond dissociation energy and the electrostatic potential distribution of Steviol reveal its antioxidant behavior. Docking studies were performed to evaluate the feasibility of this molecule to interact with antiapoptotic protein BCL-2. However, no hydrogen bonds were found in the pocket site, instead six interactions, including alkyl and π-alkyl type were formed, suggesting that the possible most feasible mechanism for anticancer activity would be through free radicals scavenging.
Identification of natural diterpenes isolated from Azorella species targeting dispersin B using in silico approaches
A bacterial biofilm is a cluster of bacterial cells embedded in a self-produced matrix of extracellular polymeric substances such as DNA, proteins, and polysaccharides. Several diseases have been reported to cause by bacterial biofilms, and difficulties in treating these infections are of concern. This work aimed to identify the inhibitor with the highest binding affinity for the receptor protein by screening various inhibitors obtained from Azorella species for a potential target to inhibit dispersin B. This work shows that azorellolide has the highest binding affinity (− 8.2 kcal/mol) among the compounds tested, followed by dyhydroazorellolide, mulinone A, and 7-acetoxy-mulin-9,12-diene which all had a binding affinity of − 8.0 kcal/mol. To the best of our knowledge, this is the first study to evaluate and contrast several diterpene compounds as antibacterial biofilm chemicals. Methods: Here, molecular modelling techniques tested 49 diterpene compounds of Azorella and six FDA-approved antibiotics medicines for antibiofilm activity. Since protein-like interactions are crucial in drug discovery, AutoDock Vina was initially employed to carry out structure-based virtual screening. The drug-likeness and ADMET properties of the chosen compounds were examined to assess the antibiofilm activity further. Lipinski’s rule of five was then applied to determine the antibiofilm activity. Then, molecular electrostatic potential was used to determine the relative polarity of a molecule using the Gaussian 09 package and GaussView 5.08. Following three replica molecular dynamic simulations (using the Schrodinger program, Desmond 2019-4 package) that each lasted 100 ns on the promising candidates, binding free energy was estimated using MM-GBSA. Structural visualisation was used to test the binding affinity of each compound to the crystal structure of dispersin B protein (PDB: 1YHT), a well-known antibiofilm compound.
A computational predicting of possible inhibitors of the main SARS-CoV-2 protease found in Algerian herbal medicines
COVID-19 is a zoonotic viral disease caused by the SARS-CoV-2 virus. Its abrupt outbreak has caused a tremendous challenge to public health systems due to the rapid spread of the virus. In this sense, a great deal of work has been focused on finding substances from herbal plants to be used against this virus. In order to investigate the molecular interactions between natural metabolites from Algerian herbal plants and the SARS-CoV-2 protease Mpro, computational docking and molecular dynamics were used, also the drug likeness degree and in silico ADMET prediction were carried out in this study. warfarin and catalponol preferentially binds to a pocket of the SARS-Cov-2 Mpro active site that is made up of residues His 41 to Glu 166 and Leu 27 to His 163 with a relatively low binding energy of -7.1 and -6.6 kcal/mol respectively. Dynamic molecular assay further established that only warfarin managed to stay in the active site. The results suggest that warfarin may be an interesting candidate for development as a medical treatment of COVID-19 and more research is proposed, without disregarding its toxicity which deserves to be well studied.
Computational study of the binding mode, action mechanism and potency of pregabalin through molecular docking and quantum mechanical descriptors
In the present study, we performed a computational study to gain insights on the binding mode and high affinity of pregabalin, its inactive isomer (R-pregabalin) and gabapentin when modulating voltage-gated calcium channels. Quantum chemical descriptors were evaluated at two different levels of theory (ωB97XD and B3LYP-D3) for the three molecules. The results show that the three ligands have similar quantum chemical descriptors, suggesting that the affinity is governed by the binding pose and the ability to access the pocket. The binding mode analysis of pregabalin indicates that it is interacting with 12 residues (6 hydrogen bonds) including Arg217, which is key to pregabalin action mechanism. Our results suggest that the electrostatic interactions and the hydrogen bonds between pregabalin and Arg217 could explain its high affinity, highlighting the importance of Arg217 in the pharmacological action.
Molecular docking and molecular dynamics studies of SARS-CoV-2 inhibitors: Crocin, digitoxigenin, beta eudesmol and favipiravir: comparative study
In this study, Crocin, Digitoxigenin, Beta-Eudesmol, and Favipiravir were docked in the active site of SARS-CoV-2 main protease (PDB code: 6LU7). The docking study was followed by Molecular Dynamics simulation. The result indicates that Crocin and Digitoxigenin are the structures with the best affinity in the studied enzyme's binding site. Still, Molecular Dynamics simulation showed that Digitoxigenin is the molecule that fits better in the active site of the main protease. Therefore, this molecule could have a more potent antiviral treatment of COVID-19 than the other three studied compounds.