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Phosphodiesterase10A (PDE10A) is a potential therapeutic target for the treatment of several neurodegenerative disorders.

Novel chiral derivatising agents (CDAs) such as methyl itaconate–anthracene adducts (MIAs) were reported for the absolute configuration determination of chiral secondary alcohols by the 1H NMR technique. These adducts were facilely prepared through well-known reactions, and furthermore, commercially available starting materials. According to these synthetic routes, the desired MIAs were afforded in 6 steps with 49% overall yield from dimethyl itaconate. Moreover, the represented MIAs provided significantly large differences of chemical shift values (ΔδSR). No racemisation from the tertiary characteristics of the adjacent alpha carbon was observed.

Self-assembly responsiveness to stimuli of polystyrene-block-polyisoprene (PS-b-PI) diblock copolymer materials is explored by means of classical molecular dynamics (MD) and dissipative particle dynamics (DPD) simulations. A concerted relationship between the parameters achieved from atomistic and DPD simulations is obtained for this molecular recognition as clearly pronounced in a phase transition. Effects of temperature, model size and composition on the morphological formation were systematically investigated for the diblock copolymeric system. Structural changes resulting in the evolution of rheology as well as an equilibrium ordered structure were analyzed in terms of order parameters and radial distribution functions. From our models, various morphologies were observed including discrete clusters (sphere-liked morphology), connected clusters (gyroid-liked morphology), hexagonally packed cylinders (HEX), connected cylinders, irregular cylinders, perfect lamellae, perforated lamellae and defected lamellae. Based on this finding, a bottom-up multi-scale simulation of the PS-b-PI diblock copolymer provides a link between equilibrium copolymeric morphologies and the crucial parameters.

The work was aimed at using Geant4-DNA software to simulate ultra-low-energy particle irradiation of DNA to understand relevant effects and fundamentals on DNA strand breaks. Light particle species of electron, hydrogen, proton, helium (He), He+ and He2+ with energy ranged in 10 – 1000 eV and fluence varied from 5 × 103 to 1 × 105 particles/cm2 irradiated DNA models, poly-AT, poly-CG and pGFP. The irradiation effect on DNA single strand breaks (SSBs) and double strand breaks (DSBs), particularly the latter, was focused. Results showed that the ratios between the numbers of SSBs and DSBs were nearly the same, independent of the particle energy and fluence. DSBs increased with increasing of ion energy, but not depended on the fluence. Discrepancies between the simulation and experiments were discussed, attributed to the simulation code overlooking the direct interaction of elastic collision between the particle and the DNA atom to cause atomic displacement.

To compare efficiency of disulfide and thiol groups in removing mercury from aqueous medium without noteworthy influence from structural differences, a series of new [Ln

Cholangiocarcinoma (CCA) is a lethal cancer with rapid progression and poor survival. Novel and more effective therapies than those currently available are, therefore, urgently needed. Our research group previously reported the combination of gemcitabine and cytotoxic T lymphocytes to be more effective than single-agent treatment for the elimination of CCA cells. However, gemcitabine treatment of CCA cells upregulates the expression of an immune checkpoint protein (programmed death-ligand 1 [PD-L1]) that consequently inhibits the cytotoxicity of T lymphocytes. To overcome this challenge and take advantage of PD-L1 upregulation upon gemcitabine treatment, we generated recombinant PD-L1xCD3 bispecific T cell engagers (BiTEs) to simultaneously block PD-1/PD-L1 signaling and recruit T lymphocytes to eliminate CCA cells. Two recombinant PD-L1xCD3 BiTEs (mBiTE and sBiTE contain anti-PD-L1 scFv region from atezolizumab and from a published sequence, respectively) were able to specifically bind to both CD3 on T lymphocytes, and to PD-L1 overexpressed after gemcitabine treatment on CCA (KKU213A, KKU055, and KKU100) cells. mBiTE and sBiTE significantly enhanced T lymphocyte cytotoxicity against CCA cells, especially after gemcitabine treatment, and their magnitudes of cytotoxicity were positively associated with the levels of PD-L1 expression. Our findings suggest combination gemcitabine and PD-L1xCD3 BiTE as a potential alternative therapy for CCA.

Domain 1 of CD147 participates in matrix metalloproteinase (MMP) production and is a candidate for targeted therapy to prevent cancer invasion and metastasis. A functional mouse anti-CD147 monoclonal antibody, M6-1B9, was found to recognize domain 1 of CD147, and its respective mouse single-chain variable fragment (ScFvM61B9) was subsequently generated. The EDLGS epitope candidate for M6-1B9 was identified using the phage display peptide technique in this study. For future clinical applications, humanized ScFv specific to domain 1 of CD147 (HuScFvM61B9) was partially adopted from the hypervariable sequences of parental mouse ScFvM61B9 and grafted onto suitable human immunoglobulin frameworks. Molecular modelling and simulation were performed in silico to generate the conformational structure of HuScFvM61B9. These results elucidated the amino acid residues that contributed to the interactions between CDRs and the epitope motif. The expressed HuScFvM61B9 specifically interacted with CD147 at the same epitope as the original mAb, M6-1B9, and retained immunoreactivity against CD147 in SupT1 cells. Binding affinity of HuScFvM61B9 by biolayer interferometry was higher than the predicted one. should be considered a potential therapeutic antibody. As domain 1 is responsible for cancer invasion and metastasis, HuScFvM61B9 would be a candidate for cancer targeted therapy in the future.

Phosphodiesterase10A (PDE10A) is a potential therapeutic target for the treatment of several neurodegenerative disorders. Thus, extensive efforts of medicinal chemists have been directed toward developing potent PDE10A inhibitors with minimal side effects. However, PDE10A inhibitors are not approved as a treatment for neurodegenerative disorders, possibly due to the lack of research in this area. Therefore, the discovery of novel and diverse scaffolds targeting PDE10A is required. In this study, we described the identification of a new PDE10A inhibitor by structure-based virtual screening combining pharmacophore modelling, molecular docking, molecular dynamics simulations, and biological evaluation. Zinc42657360 with a cyclopenta[4,5]thieno[2,3

Assembly and budding in the late-stage of human immunodeficiency virus type 1 (HIV-1) production relies on the polymerization of Gag protein at the inner leaflet of the plasma membrane. We previously generated an ankyrin repeat protein (Ank1D4) that specifically interacts with the CAp24 protein. This study aimed to improve the binding activity of Ank1D4 by generating two platforms for the Ank1D4 dimer. The design of these constructs featured a distinct orientation of monomeric Ank1D4 connected by a linker peptide (G S) . The binding surfaces in either dimer generated from the C-terminus of the Ank1D4 monomer linked with the N-terminus of another monomer (Ank1D4 ) or its inverted form (Ank1D4 ), similar to monomeric Ank1D4. The interaction of Ank1D4 with CAp24 from capture ELISA was significantly greater than that of Ank1D4 and the parental Ank1D4. The bifunctional characteristic of Ank1D4 was further demonstrated using sandwich ELISA. The binding kinetics of these ankyrins were evaluated using bio-layer interferometry analysis. The K of Ank1D4 , Ank1D4 and monomeric Ank1D4 was 3.5 nM, 53.7 nM, and 126.2 nM, respectively. The dynamics of the interdomain linker and the behavior of ankyrin dimers were investigated in silico. Upon the binding distance calculation from the candidate structures, the achievement in obtaining double active sites is more possible in Ank1D4 . The CD spectroscopic data indicated that secondary structure of dimer forms resemble Ank1D4 monomer α-helical content. This finding confers the strategy to generate dimer from rigid scaffold for acquiring the binding avidity.

Domain 1 of CD147 participates in matrix metalloproteinase (MMP) production and is a candidate for targeted therapy to prevent cancer invasion and metastasis. A functional mouse anti-CD147 monoclonal antibody, M6-1B9, was found to recognize domain 1 of CD147, and its respective mouse single-chain variable fragment (ScFvM61B9) was subsequently generated. The EDLGS epitope candidate for M6-1B9 was identified using the phage display peptide technique in this study. For future clinical applications, humanized ScFv specific to domain 1 of CD147 (HuScFvM61B9) was partially adopted from the hypervariable sequences of parental mouse ScFvM61B9 and grafted onto suitable human immunoglobulin frameworks. Molecular modelling and simulation were performed in silico to generate the conformational structure of HuScFvM61B9. These results elucidated the amino acid residues that contributed to the interactions between CDRs and the epitope motif. The expressed HuScFvM61B9 specifically interacted with CD147 at the same epitope as the original mAb, M6-1B9, and retained immunoreactivity against CD147 in SupT1 cells. The reactivity of HuScFvM61B9 was confirmed using CD147 knockout Jurkat cells. In addition, the inhibitory effect of HuScFvM61B9 on OKT3-induced T-cell proliferation as M6-1B9 mAb was preserved. As domain 1 is responsible for cancer invasion and metastasis, HuScFvM61B9 would be a candidate for cancer targeted therapy in the future.

Novel chiral derivatising agents (CDAs) such as methyl itaconate-anthracene adducts (MIAs) were reported for the absolute configuration determination of chiral secondary alcohols by the

Visible light-active BiVO4 photocatalyst was successfully synthesized through a cyclic microwave irradiation method without further calcination process. The synthesized powder was characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and UV-Vis diffuse reflectance spectroscopy (UV-Vis DRS). The BiVO4 powder revealed an excellent photocatalytic degradation of methylene blue under visible light irradiation. The degraded methylene blue was monitored by both UV-Vis spectrophotometer and absorbance in RGB channels. Similar decolorization percentage as well as pseudo first-order rate constant were achieved with high accuracy and sensitivity. The light absorption in RGB channels is an alternative simple and cartable way requiring lower amount of sample for detecting the dye degradation photocatalytic activity.

Meso-scale simulations have been widely used to probe aggregation caused by structural formation in macromolecular systems. However, the limitations of the long-length scale, resulting from its simulation box, cause difficulties in terms of morphological identification and insufficient classification. In this study, structural knowledge derived from meso-scale simulations based on parameters from atomistic simulations were analyzed in dissipative particle dynamic (DPD) simulations of PS-b-PI diblock copolymers. The radial distribution function and its Fourier-space counterpart or structure factor were proposed using principal component analysis (PCA) as key characteristics for morphological identification and classification. Disorder, discrete clusters, hexagonally packed cylinders, connected clusters, defected lamellae, lamellae and connected cylinders were effectively grouped.

Self-assembly responsiveness to stimuli of polystyrene-block-polyisoprene (PS-b-PI) diblock copolymer materials is explored by means of classical molecular dynamics (MD) and dissipative particle dynamics (DPD) simulations. A concerted relationship between the parameters achieved from atomistic and DPD simulations is obtained for this molecular recognition as clearly pronounced in a phase transition. Effects of temperature, model size and composition on the morphological formation were systematically investigated for the diblock copolymeric system. Structural changes resulting in the evolution of rheology as well as an equilibrium ordered structure were analyzed in terms of order parameters and radial distribution functions. From our models, various morphologies were observed including discrete clusters (sphere-liked morphology), connected clusters (gyroid-liked morphology), hexagonally packed cylinders (HEX), connected cylinders, irregular cylinders, perfect lamellae, perforated lamellae and defected lamellae. Based on this finding, a bottom-up multi-scale simulation of the PS-b-PI diblock copolymer provides a link between equilibrium copolymeric morphologies and the crucial parameters.

Dengue virus (DENV) infection causes mild to severe illness in humans that can lead to fatality in severe cases. Currently, no specific drug is available for the treatment of DENV infection. Thus, the development of an anti-DENV drug is urgently required. Cordycepin (3′-deoxyadenosine), which is a major bioactive compound in Cordyceps (ascomycete) fungus that has been used for centuries in Chinese traditional medicine, was reported to exhibit antiviral activity. However, the anti-DENV activity of cordycepin is unknown. We hypothesized that cordycepin exerts anti-DENV activity and that, as an adenosine derivative, it inhibits DENV replication. To test this hypothesis, we investigated the anti-DENV activity of cordycepin in DENV-infected Vero cells. Cordycepin treatment significantly decreased DENV protein at a half-maximal effective concentration (EC50) of 26.94 μM. Moreover, DENV RNA was dramatically decreased in cordycepin-treated Vero cells, indicating its effectiveness in inhibiting viral RNA replication. Via in silico molecular docking, the binding of cordycepin to DENV non-structural protein 5 (NS5), which is an important enzyme for RNA synthesis, at both the methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains, was predicted. The results of this study demonstrate that cordycepin is able to inhibit DENV replication, which portends its potential as an anti-dengue therapy.

Collagen contains hydroxyproline (Hyp), which is a unique amino acid. Three collagen-derived small peptides (Gly-Pro-Hyp, Pro-Hyp, and Gly-Hyp) interacting across a lipid bilayer (POPC model membrane) for cellular uptakes of these collagen-derived small peptides were studied using accelerated molecular dynamics simulation. The ligands were investigated for their binding modes, hydrogen bonds in each coordinate frame, and mean square displacement (MSD) in the Z direction. The lipid bilayers were evaluated for mass and electron density profiles of the lipid molecules, surface area of the head groups, and root mean square deviation (RMSD). The simulation results show that hydrogen bonding between the small collagen peptides and plasma membrane plays a significant role in their internalization. The translocation of the small collagen peptides across the cell membranes was shown. Pro-Hyp laterally condensed the membrane, resulting in an increase in the bilayer thickness and rigidity. Perception regarding molecular behaviors of collagen-derived peptides within the cell membrane, including their interactions, provides the novel design of specific bioactive collagen peptides for their applications.

Conformational search for the most stable geometry connection of 16 sets of polydopamine (PDA) tetramer subunits has been systematically investigated using density functional theory (DFT) calculations. Our results indicated that the more planar subunits are, the more stable they are. This finding is in good agreement with recent experimental observations, which have suggested that PDA are composed of the nearly planar subunits that appear to be stacked together via the π–π interactions to form graphite-like layered aggregates associated with the balance of the intramolecular hydrogen bonds and steric effects from the indole and catechol moieties. Molecular dynamics (MD) simulations of 16 spherical clusters of the tetramer subunits of PDA in the gas and aqueous phase were performed at 298 K and confirmed the stability of supramolecular tetramer aggregates. The complex formation and binding energy of all 16 clusters are very strong although the shapes of the clusters in aqueous solution are not spherical and are very much different from those in the gas phase. The aggregations of all 16 clusters in aqueous solution were also confirmed from the profiles of the Kratky plot and the radius of gyration of all clusters. Our MD results in both gas phase and aqueous solution pointed out that there are high possibilities of aggregations of the 16 kinds of tetramer subunits although the conformations of each tetramer subunit are not flat. In summary, this work brings an insight into the controversial structure of PDA tetramer units and explains some of the important structural features found in the aqueous phase in comparison to the gas phase.

Histamine is one of the most basic biogenic amino-compounds, which is composed of imidazole and a flexible ethylamine side chain moiety. Histamine is known to take the form of various types of cations, free base, monocation and dication form, where its conformational change is highly sensitively to the pH conditions. The details of these changes are still controversial due to a lack of detailed information on its crystal structures. Thus, in this study, the molecular packing structures of histidine at various pH were analyzed via X-ray diffraction in combination with vibrational spectroscopy and energy calculations. A variety of molecular conformations including the tautomeric phenomenon was found to be intimately related with intra- and intermolecular hydrogen bonds. The role of the hydrogen bonds was studied also to check the possibility of high proton conductivity of histamine, as predicted by computer simulation. Consequently, the thus-predicted proton conductivity was confirmed for the first time experimentally. During the heating process, the conductivity showed the relatively high maximum value of 10−4 S cm−1 at around 60 °C, which is related to the effective proton transfer between the amino NH group of one histamine unit and the imidazole ring of another.

The most prominent feature of UV-induced photoaged skin is decreased type 1 procollagen. Increase of the TGF-β/Smad signaling through inhibition of the TβRI dephosphorylation by the GADD34-PP1c phosphatase complex represents a promising strategy for the increase in type 1 collagen production and prevention of UV-induced skin photoaging. In this study, the molecular docking and dynamics simulations, and pharmacophore modeling method were run to investigate a possible binding site as well as binding modes between apigenin, daidzein, asiaticoside, obovatol, and astragaloside IV and PP1c. Through docking study, the possible binding site for these phytochemicals was predicted as the hydrophobic (PP1-substrate binding) groove. The result indicates that PP1 is the significant target of these compounds. Moreover, the 20,000-ps MD simulations present that the binding locations and modes predicted by the docking have been slightly changed considering that the MD simulations proffer more reliable details upon the protein-ligand recognition. The MM-GBSA binding free energy calculations and pharmacophore modeling rationally identify that the highly hydrophobic surfaces/pockets at close proximity of the catalytic core are the most favorable binding locations of the herbal compounds, and that some experimental facts upon a possible mechanism of increase in collagen biosynthesis can be explained. The present study theoretically offers the reliable binding target of the herbal compounds, and therefore helps to understanding the action mechanism for natural small molecules that enhance collagen production.

Secoiridoids are bioactive compounds, which are present in plants and exhibit anti-inflammatory activity. In this work, to understand the structural basis of five secoiridoids; amarogentin, amaroswerin, gentiopicrin, sweroside, and swertiamarin for potent inhibitors of the target proteins associated with the collagen degradation pathway, namely MMP-1, MMP-3, MMP-9 and transcription factor AP-1, molecular docking, binding mode modeling, and MD simulations were carried out. The binding inhibitory effects of the secoiridoids were screened on these proteins. The obtained results in terms of binding conformation, binding free energy, protein–ligand interaction profile, structural flexibility, and binding energy decomposition of the secoiridoid inhibitors were elucidated. The molecular modeling clarified inhibitory effect on account of the five secoiridoids towards all three Matrix metalloproteinases (MMPs). Moreover, amarogentin and gentiopicrin may interfere with gene expression via binding to AP-1. Among all screened secoiridoids, amarogentin and gentiopicrin exhibited an interesting binding affinity to the MMPs and AP-1. The results suggest that amarogentin has the highest potential for application as an anti-aging agent with the MMP inhibitory and anti-transcriptional activities, even though further studies are needed to determine the anti-aging effect in vitro, in vivo and by clinical evaluation.

A series of nanoporous [LnIII4(di-nitro-BPDC)4(NO2)3(OH)(H2O)5]·n(methanol) (LnIII ​= ​PrIII, NdIII, SmIII, EuIII, GdIII, PrIII/GdIII and PrIII/EuIII; di-nitro-BPDC2- ​= ​2,2′-dinitrobiphenyl-4,4′-dicarboxylate) was synthesized and characterized. Founded on Lewis acidic LnIII possessing vacant coordination sites and functional groups of di-nitro-BPDC2-, their catalytic activities were evaluated based on the CO2 cycloaddition reactions with epoxides under ambient pressure and solvent-free conditions. Depending on catalytic conditions, satisfying turnover number and turnover frequency of 1106 and 276 h-1, respectively, could be yielded with ≥79(±4)% conversion and 87(±1)% selectivity. The correlation between the catalysis performance and structural factors is proposed on a basis of experimental and computation results. These include the restrained transportation even in the nanoporous framework and crystallographic disorder in the LnIII coordination environment. The excellent robustness of the catalysts, effects of lanthanide contraction, and synergistic activities of the heterometallic PrIII/GdIII and PrIII/EuIII catalysts are also included.

Inhibition of P-glycoprotein (P-gp)'s function may conduct significant changes in the prescription drugs' pharmacokinetic profiles and escalate potential risks in taking place of drug/herb-drug interactions. Computational modeling was advanced to scrutinize some bioflavonoids which play roles in herb-drug interactions as P-gp inhibitors utilizing molecular docking and pharmacophore analyses. Twenty-five flavonoids were utilized as ligands for the modeling. The mouse P-gp (code: 4Q9H) was acquired from the PDB. The docking was operated utilizing AutoDock version 4.2.6 (Scripps Research Institute, La Jolla, CA) against the NBD2 of 4Q9H. The result illustrated the high correlation between the docking scores and observed activities of the flavonoids and the putative binding site of these flavonoids was proposed and compared with the site for ATP. To evaluate hotspot amino acid residues within the NBD2, Binding modes for the ligands were achieved using LigandScout to originate the NBD2-flavonoid pharmacophore models. The results asserted that these inhibitors competed with ATP for binding site in the NBD2 (as competitive inhibitors) including the hotspot residues which associated with electrostatic and van der Waals interactions with the flavonoids. In MD simulation of eight delegated complexes selected from the analyzed flavonoid subclasses, RMSD analysis of the trajectories indicated the residues were stable throughout the duration of simulations.

Spontaneous spatial organization behavior and the aggregate morphology of polystyrene-block-polyisoprene (PS-b-PI) copolymer were investigated. Molecular dynamic (MD) and mesoscopic simulations using the dynamic of mean field density functional theory (DDF) were adopted to investigate the morphology changes exhibited by this block copolymer (BCP). In the mesoscopic simulations, several atoms in repeating units were grouped together into a bead representing styrene or isoprene segments as a coarse-grained model. Inter-bead interactions and essential parameters for mesoscopic models were optimized from MD simulations. Study indicated that morphology alternations can be induced in this system at annealing temperature of 393, 493, and 533 K. From our simulations, lamellar, bicontinuous, and hexagonally packed cylindrical equilibrium morphologies were achieved. Our simulated morphologies agree well with the reported experimental evidence at the selected temperature. The process of aggregate formation and morphology evolution were concretely clarified.

Spontaneous spatial organization behavior and the aggregate morphology of polystyrene-block-polyisoprene (PS-b-PI) copolymer were investigated. Molecular dynamic (MD) and mesoscopic simulations using the dynamic of mean field density functional theory (DDF) were adopted to investigate the morphology changes exhibited by this block copolymer (BCP). In the mesoscopic simulations, several atoms in repeating units were grouped together into a bead representing styrene or isoprene segments as a coarse-grained model. Inter-bead interactions and essential parameters for mesoscopic models were optimized from MD simulations. Study indicated that morphology alternations can be induced in this system at annealing temperature of 393, 493, and 533 K. From our simulations, lamellar, bicontinuous, and hexagonally packed cylindrical equilibrium morphologies were achieved. Our simulated morphologies agree well with the reported experimental evidence at the selected temperature. The process of aggregate formation and morphology evolution were concretely clarified.

Density functional theory calculations of the H 2 molecule over the Pt(111), Pt 4 Pd 5 (111), Pt 3 Ir 6 (111), and Pt 8 Ru 1 (111) surfaces were carried out to derive key properties involving interactions and electronic state of each atom. From the calculations, H 2 dissociative adsorption shows the lowest barrier in case of the Pt 3 Ir 6 (111) surface. Pt 4 Pd 5 (111) and Pt 8 Ru 1 (111) surfaces show a small energy barrier, while the Cu(111) surface is the highest energy barrier. The difference in the reactivity of H 2 molecule with the surface is pointed out by the differences in the valence electron configuration of approaching hydrogen which is also verified from the density of state curve. The electronic structure plots illustrate the substituted atoms can interact with molecular H 2 projected on the surface d-orbital.

DNA surface and DNA strand breaks of 12 base pairs of alternating poly-AT double strands of DNA in A form were investigated by Monte Carlo simulations to find the preferential binding sites and Langevin Molecular Dynamics simulations after exposure to 0.2, 20, and 200 eV carbon atoms. Final simulated structures were further optimized using the AMBER force field and details in the surface changes, the interaction between DNA and carbon and the interaction between single-stranded strand and its pair were investigated. The solvent accessible area surface and volume of DNA were determined and significant differences observed under higher energy and temperature conditions. Both simulations concluded that under the low energy irradiation and low temperature, carbon atoms could explore the surface and interact to the preferential sites at phosphate oxygen or nitrogen in base pairing, dominated by the local base pair shift in a stagger and buckle manner, while under higher energy irradiation more severe base pair shift could be caused in combination with propeller and opening manner and several bonds could be elongated to lead to DNA damage.

P-glycoprotein (P-gp) is a 170-kDa membrane protein. It provides a barrier function and help to excrete toxins from the body as a transporter. Some bioflavonoids have been shown to block P-gp activity. To evaluate the important amino acid residues within nucleotide binding domain 1 (NBD1) of P-gp that play a key role in molecular interactions with flavonoids using structure-based pharmacophore model. In the molecular docking with NBD1 models, a putative binding site of flavonoids was proposed and compared with the site for ATP. The binding modes for ligands were achieved using LigandScout to generate the P-gp–flavonoid pharmacophore models. The binding pocket for flavonoids was investigated and found these inhibitors compete with the ATP for binding site in NBD1 including the NBD1 amino acid residues identified by the in silico techniques to be involved in the hydrogen bonding and van der Waals (hydrophobic) interactions with flavonoids. These flavonoids occupy with the same binding site of ATP in NBD1 proffering that they may act as an ATP competitive inhibitor.

Photocatalytic property of titanium dioxide and zinc oxide was used in several of application in the environmental field due to their high oxidation power and a self-sensitized degradation in a wide range of organic compound. Unfortunately, the large band gap of these metal oxides absorbs only UV radiation and limits the photocatalytic efficiency results in high cost of photocatalytic degradation of environmental pollutant. To be used under visible light irradiation, time-dependent density functional theory was applied to study anatase titanium dioxide (101) and wurtzite zinc oxide (001) with modified organic materials. Four modified structures, including polyisoprene ring, polyisoprene chain, polyacethylene, and polyphenylenevinylene, were investigated. The electronic structure and simulated UV-Vis spectra were analyzed.

Modulation of P-glycoprotein (P-gp)’s function may lead to significant changes in the prescription drugs’ pharmacokinetic profiles and increase potential risks in occurring of drug-drug including herb-drug interactions. This computational structured-based study aimed to screen bioflavonoids which play a role in herb-drug interactions as a P-gp inhibitor utilising molecular docking analysis. 25 flavonoids were used as ligands for docking study. The mouse P-gp (code: 4Q9H) was acquired from the Protein Data Bank (PDB). Docking analysis was operated utilising AutoDock 4.2.6. A lowest estimated free energy of binding value in a cluster of each flavonoid against nucleotide-binding domain 1 (NBD1) of P-gp was analysed. The result points out the high correlation between the estimated free energies of binding and percentage of inhibitory efficiency values of flavonoids applied in the molecular modelling that is powerful and capable to predict potential P-gp interactions among flavonoids and its substrates.