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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.

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.

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.

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.

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.

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.

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.

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.

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.

Improvement of adhesion between epoxy based post and composite resin core materials by low temperature plasma is an on-going dental material development. To systematically investigate the effects of surface change on the material’s chemical and mechanical properties, three series of two component materials, epoxy/urethane dimethacrylate (UDMA), epoxy/polyethylene (PE), and epoxy/poly(methylmethacrylate) (PMMA), were compared with dental epoxy based post/composite resin core. Each dual-materials system was modeled at an atomistic level. A molecular dynamics (MD) method with COMPASS force field was employed to simulate the most probable functionalization and the materials physical properties changes. Material surface modification was modeled and optimized using quantum calculations based on experimental characterization. To validate calculation results, the effect of plasma treatment on the mechanical properties of the dental post materials were examined by tensile pull out test.

BaCrO4 microdiscs composed of multi-layered microplates were successfully synthesized by a facile oxalate-assisted precipitation method for the first time. Herein, the oxalate ion helps slow down the nucleation rate of BaCrO4 crystals by complexing with the barium ion and offers control over the crystal growth and self-assembly processes via selective adsorptions probably on the facets containing elevated barium ions of the growing BaCrO4 crystals. Based on the time-dependent experiments, the dissolution–recrystallization–self-assembly process has been proposed for a possible formation mechanism of the multi-layered microdiscs. A preliminary photocatalytic study suggests that the multilayered microdiscs preferentially degrade methyl orange over methylene blue and phenol due to their positive surface charge. Further investigation on the MO degradation performance under UV and visible irradiations clearly shows that the three-dimensional hierarchical structure provides better photocatalytic activity than its low-dimensional counterpart, potentially due to its higher optical absorption ability originating from the unique morphology. The synthetic method developed in this work not only provides a one-step, facile and effective control over the morphology of BaCrO4, but also offers an alternative approach toward the design of efficient photocatalytic materials.

Clarification of proton transfer mechanisms is crucial to the development of proton exchange membrane fuel cells (PEMFCs). Nitrogen-containing heterocyclic compounds ( e.g. , imidazole derivatives) are well known for their potential to assist proton hopping through hydrogen bond networks at high temperatures. Among the many imidazole derivatives reported thus far, 1,3,5-tri(2-benzimidazolyl)benzene (TBIB) is assumed to be one of the most promising imidazole derivatives because of its triple-stranded three-dimensional hydrogen bond network. In fact, TBIB immersed into a polyphosphoric acid matrix was reported to enhance the proton conductivity to 10 −2 –10 −1 S/cm in the high-temperature range up to 170 °C. In the present work, the proton transfer mechanism has been investigated using density functional theory (DFT) with a DNP basis set and the GGA exchange-correlation functional BLYP and molecular dynamics simulations (MD) to provide insight into the cause of the remarkable proton conductivity of TBIB. Transition states in the proton hopping process were obtained using two types of models constructed from the X-ray crystal structure: an isolated two-molecule system (type I) and a periodic three-molecule system (type II). Alterations of charge distribution, molecular conformation and molecular orientation were investigated from these models. Further, the diffusion coefficient of proton transfer has been estimated and the mechanisms along three specific channels that favor efficient proton transfer between the layers have been examined in detail. Additionally, the effect of an electric field perturbation was investigated for these two models. The application of an external electric field was found to affect the proton hopping process remarkably, as evidenced by large changes in the activation energies and proton hopping times. In conclusion, the highly organized hydrogen-bonding network observed for TBIB was found to be a key factor in enhancing the efficiency of proton transfer.

Among the total of 146 volatiles extracted by SPME from the headspace of some black and white rice bran samples, twenty-eight terpenoid odorants were acculately identified. Most of these terpenoids possess good aroma character and are varied among three groups of Thai rice; black glutinous, black non-glutinous, and white non-glutinous. Of these three groups, black non-glutinous rice contains the greater number of these monoterpenoids. However, the content of the major terpenoid odorants, which are limonene, trans-β-ocimene, β-cymene, and linalool, is the highest in the bran of white Thai jasmine rice, Khao Dawk Mali 105 (KDML 105). An herbaceous odorant, myrcene, occurs in the bran of all black rice varieties but not in the bran of white rice. The flavor type of rice bran using these rice bran terpenoids was successfully classified using the chemometric principle component analysis method.

Ligustrum lucidum secoiridoid glucosides have been demonstrated to treat various types of diseases such as inflammation, pain, hepatotoxicity and hyperlipidermic as well as tonic for liver and kidney. Matrix metalloproteinases (MMPs) play a key role upon the pathology of photoaging. The present computational study showed that among the six secoiridoid glucosides (ligustroside, lucidumoside A, lucidumoside C, neonuezhenide, oleoside dimethylester, and oleuropein), ligustroside and lucidumoside A competitively inhibit all MMP-1, MMP-3, and MMP-9 activities in the docking models. The molecular docking analysis revealed a network of interactions between MMP-1, MMP-3, and MMP-9 and the ligands; ligustroside and lucidumoside A, and oxygen-containing and hydrophobic functional groups appear to be responsible for these enhanced interactions. The effect of ligustroside and lucidumoside A on the transcription factor AP-1 action was also investigated using molecular docking and dynamics simulations. The experiments suggested that inhibition of an AP-1-DNA complex formation could be on account of the direct interference of AP-1 binding onto the DNA binding sequence by ligustroside and lucidumoside A. The results suggest that both compounds have the highest potential for application as an anti-aging agent with the MMP inhibitory and anti-transcriptional activities.

Synaptotagmin 1 (Syt1) is the Ca2+ sensor protein with an essential role in neurotransmitter release. Since the wrinkle formation is due to the excessive muscle fiber stimulation in the face, a helpful stratagem to diminish the wrinkle line intenseness is to weaken the innervating neuron activity through Syt1 inhibition which is one of the possible therapeutic strategies against wrinkles. Recently, experimental evidence showed that botox-like peptides, which are typically used as SNARE modulators, may inhibit Syt1. In this work, we applied molecular modeling to (1) characterize the structural framework and (2) define the atomistic information of the factors for the inhibition mechanism. The modeling identified the plausible binding cleft able to efficiently bind all botox-like peptides. The MD simulations revealed that all peptides induced significant Syt1 rigidity by binding in the cleft of the C2A-C2B interface. The consequence of this binding event is the suppression of the protein motion associated with conformational change of Syt1 from the closed form to the open form. On this basis, this finding may therefore be of subservience for the advancement of novel botox-like molecules for the therapeutic treatment of wrinkle, targeting and modulating the function of Syt1.

Through this letter to the editor (Rebuttal), we had given our explanation for the queries raised by Professor Juan J. Melendez commenting on the high substitution energies, the small simulation supercells, and the inconsistence of experimental data and simulation results. We agree with the comment that applying a “chemical potential diagram” is a general way to study defect system. However, there are some experimental concerns on “what the initial materials should be used”, whereas many degrees of freedom become feasible. Therefore, the formation energy equation (with foreign atoms substitution) cannot be trivially answered by the formation energy within a chemical potential diagram framework, unlike substitution energy calculated directly from our suggested chemical equation. We explain in the details on our approach and confirm the validity of our main equation; FeO+Ba 8 Ti 8 O 23 →Ba 8 Ti 7 FeO 23 +TiO 2 for the substitution energy with 2×2×2 supercell size which the results still show some suggestive trends.

The investigation of structural and electric properties of doped perovskite barium titanate (BaTi0.6Ni0.2Fe0.1O3) was carried out in this study. All possible structures were generated and assessed. The change in octahedral hole geometry and electronic structure were calculated and evaluated using density functional theories (DFT) with LDA/PWC functions. The results indicate the distortion of octahedral hole of iron and its neighboring site. In addition, the direction of strain induced vectors was analyzed and located.

The structural and vibrational properties of doped and non-doped tetragonal barium titanate were predicted from density functional theories (DFT) with LDA and GGA/PW91. The doped structures were doped with niobium ion (Nb5+) and ferrous (Fe2+) that substitute at the titanium sites. All possible structures were generated and assessed. The results indicate that the splitting of phonon modes was observed in doped structures which have been considered responsible for the ferroelectric instability.

The site predilection and effects of the impurity in the form of Fe (II) and Fe (III) in the tetragonal barium titanate lattice were systematically determined by density function theory calculations. All electron calculation was carried out in the local density approximation (LDA). It is shown that both Fe (II) and Fe (III) prefer to substitute at the titanium site with oxygen vacancy compensation as a result of lowest substitution energy. Effect of Fe dopant both in form of Fe (II) and Fe (III) at titanium site with oxygen vacancy compensation lead to change in electrical property in terms of energy band structure of the tetragonal barium titanate lattice.

Proton transfer is a governing factor in the proton exchange efficiency in membrane fuel cells (PEMFCs), which are an alternative environmentally friendly resource. To develop the capacity of the PEMFC system, anhydrous membranes containing imidazole groups have garnered much interest. In this research, the relationship between the hydrogen bond networks, including the consequent packing structure, and the proton conductivity of water and imidazole (Im) systems have been systematically studied. The effect of external electrostatic perturbation was investigated in (H 2 O)H + ⋯H 2 O, (Im)H + ⋯Im, bulk water, and imidazole superlattice systems. In all of these cases, the application of an electric field in a direction opposite to that of the overall system dipole significantly reduces the activation barrier for proton transport. In isolated systems, (H 2 O)H + ⋯H 2 O and (Im)H + ⋯Im, the preferred orientation angle between the neighbouring molecules was 90°. From density functional molecular dynamics simulations of the bulk system, the proton diffusion coefficient was found to increase under the perturbation by the applied electric fields in range of 1.29 × 10 7 to 3.86 × 10 7 V cm −1 (0.0025–0.0075 a.u.) for both water and imidazole. To trace the efficient proton transfer, the proton movement trajectory was explicitly analysed in detail. Interestingly, a tilted proton hopping direction was found for imidazole crystal.

In this work, molecular docking, pharmacophore modeling and molecular dynamics (MD) simulation were rendered for the mouse P-glycoprotein (P-gp) (code: 4Q9H) and bioflavonoids; amorphigenin, chrysin, epigallocatechin, formononetin and rotenone including a positive control; verapamil to identify protein-ligand interaction features including binding affinities, interaction characteristics, hot-spot amino acid residues and complex stabilities. These flavonoids occupied the same binding site with high binding affinities and shared the same key residues for their binding interactions and the binding region of the flavonoids was revealed that overlapped the ATP binding region with hydrophobic and hydrophilic interactions suggesting a competitive inhibition mechanism of the compounds. Root mean square deviations (RMSDs) analysis of MD trajectories of the protein-ligand complexes and NBD2 residues, and ligands pointed out these residues were stable throughout the duration of MD simulations. Thus, the applied preliminary structure-based molecular modeling approach of interactions between NBD2 and flavonoids may be gainful to realize the intimate inhibition mechanism of P-gp at NBD2 level and on the basis of the obtained data, it can be concluded that these bioflavonoids have the potential to cause herb-drug interactions or be used as lead molecules for the inhibition of P-gp (as anti-multidrug resistance agents) via the NBD2 blocking mechanism in future.

Nafion, a polymer electrolyte membrane of a fuel cell, can be modified by low energy Ar + beam bombardment to increase its interfacial area with a catalyst. Recent experiments indicated that the sputtered sulfonate could lead to a decrease of hydrophilicity of Nafion when bombarded by a low energy Ar + beam. To investigate the surface modification at the atomic level, molecular dynamic (MD) simulations and experiment were carried out. The effects of Ar + at 0.5–3.0 keV, and doses in the range of 10 14 –10 15 ions cm − 2 on the damage of the Nafion surface after bombardment were deduced from the simulations. This was assessed through both the chemical and physical changes of the Nafion side chain. The potential dissociation of the C S bond after bombardment was analyzed in terms of the elongated bond population. The percentage of the extended C S bond in the system was calculated to determine the possibility of sulfonate sputtering. Real-time determination of the amount of molecular species defragged under Ar + ion bombardment by quadrupole mass spectroscopy (QMS) was used. The percentage of the amount of potentially broken C S bonds after bombardment derived from MD simulations was found in a correlation with sputtering of SO 3 − fragments obtained from the experiments. The calculated results confirm the thresholds at 2.0 keV as observed in experiment.

In order to promote understanding of the fundamentals of ultra-low-energy ion interaction with DNA, molecular dynamics simulations using combined quantum-mechanics/molecular-mechanics of poly-AT and poly-GC A-DNA double strands irradiated by

A five percent by weight of carboxylic acid terminated perfluoropolyether hybrid with silica (Krytox-Silica) in Nafion composite polymer was used in the modification of a polymer electrolyte fuel cell membrane in order to improve its efficiency at high operating temperatures. Molecular dynamics (MD) simulations were carried out in order to understand the microscopic properties of two systems, Krytox-Silica in Nafion and pure Nafion. A model of five percent Krytox-Silica in a Nafion composite polymer consisting of 15 Nafion side chains, 15 hydronium ions and one of Krytox-Silica was used. In another system, pure Nafion was modeled without Krytox-Silica. Models with various amounts of water molecules and temperatures were simulated to study the water content and temperature effects. The results were in good agreement with the experiments and could be used to describe the application of Krytox-Silica–Nafion composite at high temperatures. The effect of the amount of water molecules on the diffusion coefficient or proton conductivity showed more deviations between 5% wt of Krytox-Silica–Nafion composite and pure Nafion system at lower water content (or higher temperature) than at high water content (or low temperature). According to the diffusion coefficient results, the percentage of water molecules at each temperature corresponded to the known experimental trend. Silica, as the water absorbent in the hybrid polymer membrane, did not have a strong interaction with water molecules or H3O+ ions; thus the proton conductivities will not be highly affected by adding Krytox-Silica to the Nafion.

Nevirapine (NVP) and its structurally related analogs including nicotinamide (NAM), benzamide (BZM) and benzophenone (BZP) were used as templates in the synthesis of molecularly imprinted polymers for NVP. Molecular modeling was used to estimate binding energy of the complex formation between methacrylic acid (MAA) monomer and the selected templates, while equilibrium binding studies were applied to evaluate the polymer binding efficiency. The data indicated that NAM is the best candidate to prepare MIPs for retaining NVP due to a relatively similar binding energy between the NVP–MAA and NAM–MAA complex. The NAM-imprinted polymer showed a high binding affinity and selectivity toward NVP. When the polymer was applied as a sorbent in solid-phase extraction of NVP from human plasma, high recovery and reproducibility were obtained.

The syntheses of methylenolactocin, nephrosterinic acid and their derivatives can be achieved by using the efficient diastereoselective acylation of dimethyl itaconate–anthracene adduct followed by tandem chemoselective reduction–lactonization.

The molecular structures of the binding between human immunodeficiency virus-1 protease (HIV-1PR) and various inhibitors including existing extensive natural products extracts have been investigated for anti-HIV drug development. In this study, the binding of HIV-1PR and a terpenoid from Litchi chinensis extracts (3-oxotrirucalla-7,24-dien-21-oic acid) was investigated in order to clarify the inhibition effectiveness of this compound. Molecular dynamics (MD) simulations of HIV-1PR complex with 3-oxotrirucalla-7,24-dien-21-oic acid were performed including water molecules. The MD simulation results indicated the formation of hydrogen bonds between the oxygen atoms of the inhibitor and the catalytic aspartates, which are commonly found in inhibitors–protease complexes. On the other hand, no hydrogen bonding of this particular inhibitor to the flap region was found. In addition, the radial distribution function of water oxygens around the catalytic carboxylate nitrogens of Asp29 and Asp30 suggests that at le...

In order to understand the mechanisms of ligand binding and interaction between two commercial drugs (ligands), zanamivir and oseltamivir and H5N1 Influenza Virus Neuraminidase subtype N1, a three-dimensional model of N1-ligand (GenBank accession no. AAS654617) was initially generated by homology modeling using the 13 high-resolution X-ray structures of neuraminidase N2 and N9 as the template. With the aid of the molecular mechanics and molecular dynamics methods, the final implicit solvent refined model was obtained. It was, then, assessed by PROCHECK, PROSA and VERIFY3D. With this model, a flexible docking study was performed. The results show strong hydrogen bond interactions between the glycerol side chains of zanamivir and Arg29 of the N1. Common hydrogen bonds between the carboxyl groups and Arg279 were found for both drugs. It was also found that the Glu30, Asp62, Arg63, Arg204, Trp310, Tyr313, Glu336, Ile338, Trp348, Ala349 were observed to facilitate the enzyme-ligand non-bonding interactions as ...

Crystal structure of a three-arm model compound of poly(m-phenylene isophthalamide) (PMIA), N,N',N' '-triphenyl trimesamide Phi(CONHPhi)(3), has been analyzed by the X-ray diffraction method. The torsional angles around the bonds connecting the amide group and the central benzene ring are 24-34 degrees , almost the same as those observed for many kinds of aromatic amide compounds, reflecting mainly the intramolecular energetic balance between the amide and benzene groups. On the other hand, the torsional angles around the bonds connecting the amide group and the outer benzene ring were found to distribute over a wide range of 2-51 degrees due to the additional effect of intermolecular interactions. This is the first example to show experimentally clearly the role of intra- and intermolecular interactions in the control of torsional angle around the benzene-amide linkage. The hydrogen bonds are formed between the amide groups of the neighboring molecules, resulting in the construction of three-dimensional network structure. The local packing structure of the three-arm compound was found to be essentially the same as those observed for PMIA and the linear model compounds, indicating a characteristic structural feature of the meta-linkage-type aromatic amide compounds. The energy calculation was made using the software Polymorph Predictor to extract the energetically most stable crystal structure, which was compared successfully with the X-ray analyzed structure.

Crystal structures have been predicted by using a software Polymorph Predictor and compared with those analyzed by X-ray method for a series of low-molecular-weight aromatic amide compounds as models of poly(m-phenylene isophthalamide) and poly(p-phenylene terephthalamide). For most of the compounds investigated here, the predicted crystal structure of the lowest or the next lowest packing energy has been found to be in good agreement with the X-ray analyzed structure. However, the energy difference was not very large between these energetically most plausible structures and the other less stable candidates, indicating a difficulty of unique prediction of 3D molecular packing structure and a possibility of existence of various types of crystal modification.

Molecular and crystal structures of a series of model compounds of poly(m-phenylene isophthalamide) have been analyzed by the X-ray diffraction method and the various types of 3-D hydrogen bond network structures have been clarified. The twisting angles between benzene and amide groups are in the range of 25−40°, which is common to all of the analyzed model compounds and the parent polymer itself and could be reproduced well by the energy calculation with the nonbonded interatomic interactions between the benzene and amide groups taken into consideration. The molecular conformation, the packing mode of molecules, and the intermolecular hydrogen bond network structure were found to have good correlation with each other and could be classified systematically into several groups. This classification should be important for the energetic interpretation of the formation mechanism of the 3-D hydrogen bond network structure.

Cyanine dyes have been widely used as a fluorescence probe for biomolecules and protein labeling. The mostly used cyanine dyes for nucleic acids labeling are DiSC2(3), DiSC2(5), and DiSC2(7). The possible structures and binding energies of RNA-RNA/Cyanine dyes were predicted theoretically using AutoDock Vina. The results showed that cyanine dyes and bases of RNA-RNA have the van der Waals and pi-pi interactions. The maximum absorption wavelength in the visible region obtained from the TD-DFT calculations of all cyanine dyes in the absence of the RNA-RNA double strand showed the bathochromic shift.

Conformations and spectroscopic properties of laccaic acid A (lacA) were studied by means of the experimental and theoretical approaches. The minimum energy conformers of lacA in the gas phase and in implicit water obtained from the B3LYP/6-311G(d,p) calculations displayed the same orientation of the COOH and OH groups on the anthraquinone-based component. The intramolecular hydrogen bonds (H-bonds) formed between the COOH, C=O and OH groups are very strong. In contrast, the orientations of the Ph(OH)CH(2)CH(2)NHCOCH(3) substituent moiety on the anthraquinone-based component in the gas phase and in implicit water are completely different. The substituent prefers to bind with the anthraquinone-based component in the gas phase while it moves away from the anthraquinone-based component in implicit water. The calculated IR spectra of the two lowest-lying energy conformers of lacA in the gas phase fit to the experimental FTIR spectrum. The full assignments of the vibrational modes with the correlated vibrational wavenumbers of those conformers were proposed here, for the first time. The intramolecular H-bond formations in lacA can cause the shift of the vibrational wavenumber for the COOH, C=O, OH and NH groups as compared to the normal vibrations of these groups. The NMR spectra showed that the stabilities of the two lowest-lying energy conformers of lacA in the gas phase are comparable and this is consistent with their computational energies. The UV-Vis spectra of the lowest-lying energy conformers of lacA in implicit water were compared with the experimental UV-Vis spectrum. The calculations suggested that the electronic transition in the visible region involves with the singlet π→π(*) excitation which the electron density transfers to a COOH group on the anthraquinone ring.

We applied molecular dynamics simulations to investigate the binding properties of a designed ankyrin repeat protein, the DARPin–CD4 complex. DARPin 23.2 has been reported to disturb the human immunodeficiency virus (HIV) viral entry process by Schweizer et al. The protein docking simulation was analysed by comparing the specific ankyrin binder (DARPin 23.2) to an irrelevant control (2JAB) in forming a composite with CD4. To determine the binding free energy of both ankyrins, the MM/PBSA and MM/GBSA protocols were used. The free energy decomposition of both complexes were analysed to explore the role of certain amino acid residues in complex configuration. Interestingly, the molecular docking analysis of DARPin 23.2 revealed a similar CD4 interaction regarding the gp120 theoretical anchoring motif. In contrast, the binding of control ankyrin to CD4 occurred at a different location. This observation suggests that there is an advantage to the molecular modification of DARPin 23.2, an enhanced affinity for CD4.

In ion implantation in materials, when the ion energy is sufficiently low, the ion interaction with materials is in the nanoscale. When low-energy ion beam irradiates biological living materials such as cells and DNA, the nanoscaled ion interaction with the biological objects is a novelty. Theoretical calculation demonstrates the low-energy ion range in DNA being in the order of nanometer. In experiments, keV ions were applied to irradiate naked DNA to investigate primary effects of the low-energy ion interaction with DNA, which would be served as a basis for further investigations on mechanisms involved in ion beam induced mutation of biological species. Preliminary results showed that the nanoscale low-energy ion interaction with DNA could indeed induce changes in the DNA forms. DNA transfer in bacteria demonstrated mutation occurred after low-energy ion irradiation of the DNA. In computer molecular dynamics simulation, 1–100-eV ions bombarded A-DNA and revealed DNA changes occurring in nanoscale with preferential consequence.

For investigating mechanisms involved in low-energy ion beam induced mutation, besides experiments using low-energy and low-fluence ions to bombard naked DNA, molecular simulations were carried out as an effort towards the insight in molecular interactions between ions and DNA. In the current study, Monte Carlo (MC) and molecular dynamics (MD) simulations were applied. The results of MC simulations provide some clues about the interaction energies and sites of preference of N-ion bombardment on an A-DNA short duplex strand. MD simulations of a single N-ion moving towards the same DNA strand with different linear velocities corresponding to bombardment energies of 0.1, 1, 10 and 100 eV revealed information about changes in bond lengths and visibly distorted structures of bombarded nucleotides. The simulations demonstrated that ion-bombardment-induced DNA change in structure was not a random but preferential effect.