Doping of 3d Transition Metals o n Monolayer o f Graphene a nd Borophene

We Study the doping of various metallic 3d transition metal (TM) atoms like iron (Fe), Cobalt (Co), Copper (Cu) and Nickel (Ni) on monolayer of the borophene and graphene. These 2D layers show energy dispersion and metalloid properties because its band gap is very less or near to zero. We explored borophene is semi-metallic with the titled Dirac cone and graphene is semi metallic whose conduction and valence bands meets at Dirac cone. We analyzed the adsorption of 3d transition metal (TM) on the 2D layers through density functional theory (DFT) based calculations. In this paper, we observed the most suitable and acceptable adsorption site for each adatom, and calculated the binding energy per atom, density of states and magnetic moment of resulting borophene and graphene-adatom system. Here, we find that Nickel (Ni) is perfect as electron doping and iron (Fe) is the most effective for magnetically doped borophene. In the case of graphene we find that Co is most suitable for magnetically doping and Cu is best for electron doping.

In-silico characterization of phytochemicals identified from Vitex negundo (L) extract as potential therapy for Wnt-signaling proteins

Background Colorectal cancer is the third most diagnosed disease in the world population and current chemotherapy has been used for targeting the cell proliferation and metastasizing ability of tumor cells. Potent chemotherapeutic drugs for colorectal cancer are capecitabine, fluorouracil, irinotecan, etc. which have toxic effects in normal tissues and adverse effects in multiple organs leading to major obstacles in clinical use. The aim of the study is the use of plant-derived compounds that improve the effectiveness of chemotherapeutics with lower and alleviate toxic side effects and reduce the risk of tumor progression. Results The current study is performed using Vitex negundo leaf which has been demonstrated to have positive effects against colorectal cancer. The use of computational approaches will help improve the identification and screening of lead molecules using AutoDock 4.2 and AutoDock Vina. Using computational approaches will help to improve lead identification and screening. Herein, we have retrieved six phytochemicals from published literature and investigated their inhibitory effect with Wnt-associated signaling proteins. Authentication of phytocompounds and Wnt-associated signaling proteins was done using AutoDock.4.2. Conclusions The results are screened based on the number of hydrogen bonds, binding energy, and interacting amino acids. The Isoorientin, luteolin, and Chrysophanol get the highest binding energy with target receptors. The binding energy is calculated with all target receptors from the range of − 6.0 to − 8.9 kcal/mol. The In-silico drug likeliness properties are predicted to be the best interacting compounds based on Lipinski Rule of 5 and ADMET analysis. Hence, we propose that Isoorientin, luteolin, and Chrysophanol are the potential inhibitors of Wnt signaling inhibitors, and preclinical studies are needed to confirm the promising therapeutic ability of colorectal cancer.

The potency of alpha-humulene as HER-2 inhibitor by molecular docking

HER-2 overexpression is present in approximately 20% of breast cancer. This research aims to study the interactions of α-humulene to HER-2 protein by using in silico molecular docking. The experiment was carried out by HER-2 protein preparation (PDB ID 3PP0), docking validation, α-humulene optimization, and α-humulene docking. The results showed that α-humulene had binding energy of -7.50 kcal/mol, Van der Waals binding energy of -7.48 kcal/mol, and electrostatic energy of -0.02 kcal/mol. α-Humulene is potential as anti-breast cancer towards HER-2 in silico.

Optical Absorption of a D2+ Artificial Molecule Confined in a Spherical Quantum Dot

In this work, we have performed a theoretically study on the energy spectrum, binding energy and intersubband optical absorption of a D2+ complex confined in a spherical quantum dot with finite confinement potential by using diagonalization method within the effective mass approximation. We analyzed the effect of the quantum dot size and internuclear distance on the binding energy, equilibrium distance and optical response of the singly ionized double donor complex. Theoretical analysis of the D2+ system indicated that the internuclear distance significantly affects the energy difference between the two lowest-lying electron states and amplitude of the optical absorption. In general, we conclude that the internuclear distance and quantum dot size dependence of the low-lying energy spectrum of the D2+ complex in a quantum dot favors the describing of an appropriate two-level system needed for quantum computation.

Identification of Some Dietary Flavonoids as Potential Inhibitors of TMPRSS2 Through Protein-ligand Interaction Studies and Binding Free Energy Calculations

The alarming increase in COVID-19 cases and deaths calls for an urgent cost-effective pharmacological approach. Here, we examine the inhibitory activity of a group of dietary bioactive flavonoids against the human protease TMPRSS2, which plays a major role in SARS CoV-2 viral entry. After the molecular docking studies of a large number of flavonoids, four compounds with high binding scores were selected and studied in detail. The binding affinities of these four ligands, Amentoflavone, Narirutin, Eriocitrin, and Naringin, at the active site of TMPRSS2 target were investigated using MD simulations followed by MM-PBSA binding energy calculations. From the studies, a number of significant hydrophobic and hydrogen bonding interactions between the ligands and binding site amino residues of TMPRSS2 are identified which showcase their excellent inhibitory activity against TMPRSS2. Among these ligands, Amentoflavone and Narirutin showed MM-PBSA binding energy values of -155.48 and -138.13 kJ/mol respectively. Our previous studies of the inhibitory activity of these compounds against main protease of SARS-COV2 and the present study on TMPRSS2 strongly highlighted that Amentoflavone and Naringin can exhibit promising multi-target activity against SARS-CoV-2. Moreover, due to their wide availability, no side effects and low cost, these compounds could be recommended as dietary supplements for COVID patients or for the development of SARS-CoV-2 treatments.

Pharmacophore Modeling, Docking, and Molecular Dynamics Simulation of Flavonoids as Inhibitors of Urokinase-type Plasminogen Activator

The urokinase-type plasminogen activator (uPA) system plays a significant role in the invasion and metastasis of cancer cells. The present study was conducted to investigate natural product compounds as inhibitors and hit molecules of uPA using in-silico analysis. A pharmacophore model was built to screen the Indonesian Herbal Database (HerbalDB) to obtain inhibitors of different scaffolds. Based on the molecular docking score, four ligands were selected as potential uPA inhibitors. Subsequently, the stability of the ligand-uPA complex was analyzed using molecular dynamics (MD) simulation. An RMSD graph of the backbone protein and the RMSF values of the amino acid residues were also determined. In addition, the MM-PBSA method was applied to calculate the free binding energy. According to the results, Model_3, characterized by aromatic rings 23 (F1 and F2), cationic H-bond donor (F3), and metal ligator (F4) features, had an adequate goodness-of-hit score (GH). The four top-ranked ligands, isorhamnetin, rhamnetin, quercetin, and kaempferol, showed higher docking scores compared to the others. This study confirmed that isorhamnetin, rhamnetin, and kaempferol build stable complexes with uPA with lower binding energy than quercetin.

Safety, Stability, and Therapeutic Efficacy of Long-Circulating TQ-Incorporated Liposomes: Implication in the Treatment of Lung Cancer

Thymoquinone (TQ), which is one of the main bioactive constituents of Nigella sativa seeds, has demonstrated its potential against various cancer models. The poor solubility of TQ in aqueous solution limits its uses in clinical application. The present study aimed to develop a novel formulation of TQ to increase its bioavailability and therapeutic potential with minimal toxicity. Polyethylene glycol (PEG)-coated DSPC/cholesterol comprising TQ liposomes (PEG-Lip-TQ) were prepared and characterized on various aspects. A computational investigation using molecular docking was used to assess the possible binding interactions of TQ with 12 prospective anticancer drug targets. The in vitro anticancer activity was assessed in A549 and H460 lung cancer cells in a time- and dose-dependent manner, while the oral acute toxicity assay was evaluated in silico as well as in vivo in mice. TQ docked to the Hsp90 target had the lowest binding energy of −6.05 kcal/mol, whereas caspase 3 was recognized as the least likely target for TQ with a binding energy of −1.19 kcal/mol. The results showed 96% EE with 120 nm size, and −10.85 mv, ζ-potential of PEG-Lip-TQ, respectively. The cell cytotoxicity data demonstrated high sensitivity of PEG-Lip-TQ and a several fold decrease in the IC50 while comparing free TQ. The cell cycle analysis showed changes in the distribution of cells with doses. The in vivo data revealed an ~9-fold increase in the LD50 of PEG-Lip-TQ on free TQ as an estimated 775 and 89.5 mg/kg b.w, respectively. This study indicates that the pharmacological and efficacy profile of PEG-lip-TQ is superior to free TQ, which will pave the way for an exploration of the effect of TQ formulation in the treatment of lung cancer in clinical settings.

Ion-shift reagent binding energy and the shift-mass correlation in ion mobility spectrometry

Ion mobility spectrometry is widely used for the detection of illegal substances and explosives in airports, ports, custom, some stations and many other important places. This task is usually complicated by false positives caused by overlapping the target peaks with that of interferents, commonly associated with samples of interest. Shift reagents (SR) are species that selectively change ion mobilities through adduction with analyte ions when they are introduced in IMS instruments. This characteristic can be used to discriminate false positives because the interferents and illegal substances respond differently to SR depending on the structure and size of analytes and their interaction energy with SR. This study demonstrates that ion mobility shifts upon introduction of SR depend, not only on the ion masses, but on the interaction energies of the ion:SR adducts. In this study, we introduced five different SRs using ESI-IMS-MS to study the effect of the interaction energy and size on mobility shifts. The mobility shifts showed a decreasing trend as the molecular weight increased for the series of compounds ethanolamine, valinol, serine, threonine, phenylalanine, tyrosine, tributylamine, tryptophan, desipramine, and tribenzylamine. It was proved that the decreasing trend was partially due to the inverse relation between the mobility and drift time and hence, the shift in drift time better reflects the pure effect of SR on the mobility of analytes. Yet the drift time shift exhibited a mild decrease with the mass of ions. Valinol pulled out from this trend because it had a low binding energy interaction with all the SR and, consequently, its clusters were short-lived. This short lifetime produced fewer collisions against the buffer gas and a drift time shorter compared to those of ions of similar molecular weight. Analyte ion:SR interactions were calculated using Gaussian. IMS with the introduction of SR could be the choice for the free-interferents detection of illegal drugs, explosives, and biological and warfare agents. The suppression of false positives could facilitate the transit of passengers and cargos, rise the confiscation of illicit substances, and save money and distresses due to needless delays. Keywords: Adduction, ion mobility spectrometry, mass spectrometry, shift reagent, valinol, buffer gas modifier