The Computational Calculation and Molecular Docking of Aeroplysinin-1 As Antibacterial

Aeroplysinin-1 is naturally found from marine sponges as an anti-bacterial compound. Computational calculation and molecular docking were performed for aeroplysinin. Aeroplysinin as an inhibitor has optimized in the gas phase using DFT with 6-31G(d) functional. The structure from geometry optimization of aeroplysinin-1is, not in one plane. The interaction of aeroplysinin-1 with two different DNA gyrase from E. Coli and S. Aureus. In this research,aeroplysinin-1 can inhibit the protein with the free binding energy of about -5.7 kcal/mol and -6.35 kcal/mol, respectively, for E. Coli and S. Aureus. The dominant molecular interaction is the hydrogen bond.

Altered interaction between RBD and ACE2 receptor contributes towards the increased transmissibility of SARS CoV-2 delta, kappa, beta, and gamma strains with RBD double mutations

ABSTRACTThe COVID-19 pandemics by SARS-CoV-2 causes catastrophic damage for global human health. The initial step of SARS-CoV-2 infection is the binding of the receptor-binding domain (RBD) in its spike protein to ACE2 receptor in host cell membrane. The evolving of SARS-CoV-2 constantly generates new mutations across its genome including RBD. Besides the well-known single mutation in RBD, the recent new mutation strains with RBD “double mutation” is causing new outbreaks globally, as represented by the delta strain containing RBD L452R/T478K. Although it is considered that the increased transmissibility of the double mutated strains could be attributed to the alteration of mutated RBD to ACE2 receptor, the molecular details remains to be unclear. Using the methods of molecular dynamics simulation, superimposed structural comparison, free binding energy estimation and antibody escaping, we investigated the relationship between ACE2 receptor and the RBD double mutant L452R/T478K (delta), L452R/E484Q (kappa) and E484K/N501Y (beta, gamma). The results demonstrated that each of the three RBD double mutants altered RBD structure, led to enhanced binding affinity of mutated RBD to ACE2 receptor, leading to increased transmissibility of SARS-CoV-2 to the host cells.

Arylmethylene hydrazine derivatives containing 1,3-dimethylbarbituric moiety as novel urease inhibitors

A new series of arylmethylene hydrazine derivatives bearing 1,3-dimethylbarbituric moiety 7a–o were designed, synthesized, and evaluated for their in vitro urease inhibitory activity. All the title compounds displayed high anti-urease activity, with IC50 values in the range of 0.61 ± 0.06–4.56 ± 0.18 µM as compared to the two standard inhibitors hydroxyurea (IC50 = 100 ± 0.15 μM) and thiourea (IC50 = 23 ± 1.7 μM). Among the synthesized compounds, compound 7h with 2-nitro benzylidene group was found to be the most potent compound. Kinetic study of this compound revealed that it is a mix-mode inhibitor against urease. Evaluation of the interaction modes of the synthesized compounds in urease active site by molecular modeling revealed that that compounds with higher urease inhibitor activity (7h, 7m, 7c, 7l, 7i, and 7o, with IC50 of 0.61, 0.86, 1.2, 1.34, 1.33, 1.94 μM, respectively) could interact with higher number of residues, specially Arg609, Cys592 (as part of urease active site flap) and showed higher computed free energy, while compounds with lower urease activity (7f, 7n, 7g, and 7a with IC50 of 3.56, 4.56, 3.62 and 4.43 μM, respectively) and could not provide the proper interaction with Arg609, and Cys592 as the key interacting residues along with lower free binding energy. MD investigation revealed compound 7h interacted with Arg609 and Cys592 which are of the key residues at the root part of mobile flap covering the active site. Interacting with the mentioned residue for a significant amount of time, affects the flexibility of the mobile flap covering the active site and causes inhibition of the ureolytic activity. Furthermore, in silico physico-chemical study of compounds 7a–o predicted that all these compounds are drug-likeness with considerable orally availability.

Computational Study for the Evaluation of Drug Candidature of the Most Abundant Molecules from Vitex agnus-castus L. for Inhibition of HBV Capsid and X Proteins

Hepatitis B virus (HBV) infection is one of the main sources of liver disease. In this study, we use computation methods to evaluate the drug candidature of the most abundant molecules from Vitex agnus L for the inhibition of HBV capsid protein and X protein. Molecular docking analyses were performed, using Autodock Vina, PKCSM and SwissADME were used to calculate ADMET. The results showed that the free binding energy for all tested molecules is better than that of Tenofovir disoproxil, a drug used to treat HBV, using capsid protein and protein X as a target. These results indicate that these ligands bind favorably to the binding site of HBV capsid protein and protein X, which may be considered a potential ligand for treating HBV-related diseases.

Skrining Senyawa dari Tanaman Rhodomyrtus tomentosa (Aiton) Hassk terhadap SARS-CoV-2 ORF3a

The ORF3a protein from SARS-CoV has functions in terms of ion channel activity, modulates the trafficking properties of SARS-CoV spike (S) protein, increases fibrinogen expression in pulmonary epithelial cells, and induces apoptosis. So that research is needed to overcome the ORF3a experiment. The method in this research uses the computational screening method with autodok4 software. The results of this study resulted in free binding energy between Hassk Rhodomyrtus tomentosa (Aiton) and ORF3a compounds, namely: α-tocopherol-quinone (-5.86); blumeatin (-4.98); methyl cinnamate (-4.44); myricetin (-4.49); naringenin (-4.93); quercetin (-4,9); rhodomyrtone (-6); rhodomyrtosone B (-7.11); rhodomyrtosone C (-6.77); tetrahydroxyflavanone (-4.91); α-tocopherol A (-6.72); verimol K (-4.89); watsonianone A (-7.55). Based on the data obtained, the ligand with the most potential due to the stability of the bond is watsonianone A.

Study of Interaction Between Bovine Serum Albumin and Dolutegravir Intermediate: Fluorescence and Molecular Docking Analysis

Novel (4R,12aS)-7-methoxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido-[1',2':-4,5]-pyrazino[2,1-b][1,3]oxazine-9-carboxylic acid (L) was synthesized and characterised. The interaction between bovine serum albumin (BSA) with L was scrutinized by steady-state fluorescence spectroscopy, fluorescence anisotropy, fluorescence lifetime, and molecular docking methods. The fluorescence titration experiments of BSA resulted in fluorescence quenching with the incremental addition of L. The conformational binding of L to BSA has been investigated by molecular docking analysis. The molecular probe's best conformation showed the affinity as free binding energy release of -7.93 Kcal/mol. The docking analysis confirms that ligand binds in the near vicinity of TRP-213 in the binding pocket of subdomain IIA.

Insights into the Effect of Curcumin and (–)-Epigallocatechin-3-Gallate on the Aggregation of Aβ(1–40) Monomers by Means of Molecular Dynamics

In this study, we compared the effects of two well-known natural compounds on the early step of the fibrillation process of amyloid-β (1–40), responsible for the formation of plaques in the brains of patients affected by Alzheimer’s disease (AD). The use of extensive replica exchange simulations up to the µs scale allowed us to characterize the inhibition activity of (–)-epigallocatechin-3-gallate (EGCG) and curcumin (CUR) on unfolded amyloid fibrils. A reduced number of β-strands, characteristic of amyloid fibrils, and an increased distance between the amino acids that are responsible for the intra- and interprotein aggregations are observed. The central core region of the amyloid-β (Aβ(1–40)) fibril is found to have a high affinity to EGCG and CUR due to the presence of hydrophobic residues. Lastly, the free binding energy computed using the Poisson Boltzmann Surface Ares suggests that EGCG is more likely to bind to unfolded Aβ(1–40) fibrils and that this molecule can be a good candidate to develop new and more effective congeners to treat AD.

In Silico Study on Interaction and Preliminary Toxicity Prediction of Eleutherine americana Components as an Antifungal and Antitoxoplasmosis Candidate

Red bulbs of Eleutherine americana (Aubl.) Merr. ex K. Heyne has been known for its high content of naphthoquinones that have antifungal and antiparasitic activities. In this research, in silico interaction study was performed between 31 compounds reported to be found in E. americana with the selected target proteins for antifungal and antitoxoplasmosis activity using the molecular docking method. An ORPs (OSBP-related proteins), Osh4 (PDB ID: 1ZHX), and N-myristoyltransferase (Nmt, PDB ID: 1IYL) were used as the antifungal target proteins. Toxoplasma gondii purine nucleoside phosphorylase (TgPNP, PDB ID: 3MB8) and calcium-dependent protein kinase-1 (TgCDPK1, PDB ID: 4M84) were used as antitoxoplasmosis target proteins. Three-dimensional structures of the test compounds were made and optimized using GaussView 6.0 and Gaussian 09W. The target proteins were prepared using the Discovery Studio 2016 Program. Aquatic toxicity prediction as the preliminary assessment of the safety of the compounds was performed using ECOSAR v2.0. The results suggest that the compound having both the smallest free binding energy compared with positive control and other test compounds and low predicted toxicity is β-sitosterol with a free binding energy of ‒11.55 and ‒11.18 kcal/mol towards Osh4 and Nmt and ‒8.06 and ‒10.29 kcal/mol towards TgPNP and TgCDPK1, respectively.

ANTI-PARKINSON POTENTIAL OF PERSEA AMERICANA SEED EXTRACTS THROUGH IN-SILICO DOCKING STUDY

Objective: The aim of this study is to investigate the potential of Persea americana extracts for their Anti-Parkinson application through an in-silico docking study. Methods: PubChem and protein data bank databases were used to retrieve 3D structures. AutoDock4 was used to perform protein-ligand docking analysis. PyMOL was used to visualize the docking results. Results: Among the 30 ligand, the highest affinity was demonstrated by Hesperidin with a free binding energy of −6.8 kcal/mol and formation of five hydrogen bonds. The second highest significance was demonstrated by Biphenyl 4-(4-diethylaminobenzylidenamino) with a free binding energy of −5.9 kcal/mol with the formation of 2 hydrogen bonds. Among the three sets of phytochemicals from different solvent extracts, water extract demonstrated the highest potential as Anti-Parkinson active. Conclusion: P. americana extracts were analyzed for their Anti-Parkinson potential, and among the three extracts, the aqueous extract was predicted to have significant Anti-Parkinson potential, based on in silico docking analysis, due to the presence of active phytochemicals such as Hesperidin and others.

THE INTERACTION OF miR-4258, miR-3960, miR-211-3p AND miR-3155b WITH mRNAs GENES OF NON-POLYGLUTAMINE TRINUCLEOTIDE DISORDERS

Trinucleotide repeat expansion disorders constitute a group of dominantly inherited neurological diseases that are incurable and ultimately fatal. In the present work, miRNA binding sites were predicted by the MirTarget program. It was given characteristics of miRNAs binding sites in 5' and 3' UTR mRNAs genes of non-polyglutamine trinucleotide disorders with CGG, GCC, CUG repeats. Binding sites of 2567 miRNAs with mRNAs of 17494 human genes were determined. 206 genes with nucleotide repeats, mRNAs of which are bind with miRNA in the 5'UTR and 3'UTR, were observed. From thus, 2668 miRNAs binding sites are located in the 5'UTR, 3853 – in the 3'UTR with ΔG/ΔGm values equal to 85 % and more. It was found that 34 gene’s mRNA having trinucleotide (CGG\GCC\CUG) repeats were targets for miR-4258, miR-3960 miR-211-3p and miR-3155b. miR-4258 binds to mRNA of ADARB1, C11orf87 and CBFB genes with free binding energy - 93 kJ/mole and ΔG/ΔGm 91%, to mRNA of ARHGEF7, BCR, BRSK2 and C9orf91 genes with free binding energy - 91 kJ/mole and ΔG/ΔGm 89%. miR-3960 binds in GCC repeats to mRNA of ABCC1 and BLMH genes with free binding energy - 116 kJ/mole. miR-211-3p and miR-3155b interact with mRNA of ACACA and ANKRD13D genes in 5’-3’untranslated regions. Studying binding characteristics of miRNA and genes will help identify association of miRNAs with genes with trinucleotide repeats for recommending for the diagnosis of nucleotide repeat expansion disorders.