A sensitive and selective sensor for dopamine determination based on a molecularly imprinted electropolymer of o-aminophenol

A simple and reliable method was proposed for preparing a selective dopamine (DA) sensor based on a molecularly imprinted electropolymer of o-aminophenol. The sensor is selective for the determination of DA in the presence of high concentrations of ascorbic acid (AA), with a maximum molar ratio of 1/1000. The molecular imprinted (MIP) sensor was tested by cyclic voltammetry (CV) as well as differential pulse voltammetry (DPV) to verify the changes in oxidative currents of ferricyanide. In optimized conditions, DA at concentrations of 2 × 10⁻⁸ to 0.25 × 10⁻⁶ mol/L could be determined with a detection limit of 1.98 × 10⁻⁹ mol/L (S/N = 3). The MIP sensor showed high selectivity, sensitivity, and reproducibility. Determination of DA in simulated samples of dopamine hydrochloride showed good recovery.     

DFT and TD-DFT theoretical studies on photo-induced electron transfer process on [Cefamandole].C60 nano-complex

The C₆₀ fullerene displays a considerable electronegativity. It has a unique photophysical and electrochemical behavior that can be used as a suitable drug carrier. In the present study, the interaction of C₆₀ fullerene as an electron recipient with the Cefamandole antibiotic was investigated in both ground and excited states using DFT and TD-DFT methods. The study of the interaction of C₆₀ and Cefamandole via electron localization function (ELF) and reduced density gradient (RDG) revealed that the complex formation is of van der Waals type. The data from natural bonding orbitals (NBO) analysis also confirmed the interaction type. The study of absorption and emission spectrum via CAM-B3LYP in the TD-SCF state showed that the emission peak of C₆₀ fullerene in the 591.73 nm after the complex formation results in the extinction of this emission spectrum due to charge transfer (CT) from chelator to fluorophore. The photoinduced electron transfer (PET) process was investigated using the electron hole theory.     

Antiviral drug acyclovir exhibits antitumor activity via targeting βTrCP1: Molecular docking and dynamics simulation study

The critical role of βTrCP1 in cancer development makes it a discerning target for the development of small drug like molecules. Currently, no inhibitor exists that is able to target its substrate binding site. Through molecular docking and dynamics simulation assays, we explored the comparative binding pattern of βTrCP1-WD40 domain with ACV and its phospho-derivatives (ACVMP, ACVDP and ACVTP). Consequently, through principal component analysis, βTrCP1-ACVTP was found to be more stable complex by obscuring a reduced conformational space than other systems. Thus based on the residual contribution and hydrogen bonding pattern, ACVTP was considered as a noteworthy inhibitor which demarcated binding in the cleft formed by βTrCP1-WD40 specific β-propeller. The outcomes of this study may provide a platform for rational design of specific and potent inhibitor against βTrCP1, with special emphasis on anticancer activity.     

Evaluation of the combination mode of azoles antifungal inhibitors with CACYP51 and the influence of Site-directed mutation

14α-demethylase (CYP51) is an essential metabolic enzyme for fungal survival and has been considered as an interesting target for the development of new antifungal inhibitors. Azoles antifungal inhibitors in the treatment of fungal diseases are good candidates via the interaction with the target enzyme CYP51 of fungus. In the study, we constructed the homology model for Candida albicans CYP51 (CACYP51) and analyzed the active site. In order to better understand the structural characteristics of azoles inhibitors and combination mode, the common feature pharmacophore model and the molecular docking were performed. The results suggest that the azoles inhibitors consist of three chemical features: the aromatic groups, phenyl groups and the azoles groups. The aromatic groups of inhibitors occupy the upper of active pocket, the phenyl groups and azoles groups occupy the bottom of active pocket. Further validation studies found these amino acid residues Tyr118, His310 and Ser378 play an important role in the substrate binding, and these amino acid residues with site-directed mutation will weaken the combining ability of the inhibitors.     

Factors responsible for the aggregation behavior of hydrophobic polyelectrolyte PEA in aqueous solution studied by molecular dynamics simulations

Self-association (i.e. interchain aggregation) behavior of atactic poly(ethacrylic acid) PEA in dilute aqueous solution as function of degree-of-neutralization by Na⁺ counter-ions (i.e. charge fraction f) was investigated by molecular dynamics simulations. Aggregation is found to occur in the range 0 ≤ f ≤0.7 in agreement with experimental results compared at specified polymer concentration C_p = 0.36 mol/l in dilute solution. The macromolecular solution was characterized and analysed for radius-of-gyration, torsion angle distribution, inter and intra-molecular hydrogen bonds, radial distribution functions of intermolecular and inter-atomic pairs, inter-chain contacts and solvation enthalpy. The PEA chains form aggregate through attractive inter-chain interaction via hydrogen bonding, in the range f < 0.7, in agreement with experimental observation. The numbers of inter-chain contacts decreases with f. A critical structural transition occurs at f = 0.7, observed via simulations for the first time, in R_g as well as inter-chain H-bonds. The inter-chain distance increases with f due to repulsive interactions between COO− groups on the chains. PEA-PEA electrostatic interactions dominant solvation enthalpy. The PEA solvation enthalpy becomes increasingly favorable with increase in f. The transition enthalpy change, in going from uncharged (acid) state to fully charged state (f = 1) is unfavorable towards aggregate formation.     

IM-UFF: Extending the universal force field for interactive molecular modeling

The universal force field (UFF) is a broadly applicable classical force field that contains parameters for almost every atom type of the periodic table. This force field is non-reactive, i.e. the topology of the system under study is considered as fixed and no creation or breaking of covalent bonds is possible. This paper introduces interactive modeling-UFF (IM-UFF), an extension of UFF that combines the possibility to significantly modify molecular structures (as with reactive force fields) with a broad diversity of supported systems thanks to the universality of UFF. Such an extension lets the user easily build and edit molecular systems interactively while being guided by physics based inter-atomic forces. This approach introduces weighted atom types and weighted bonds, used to update topologies and atom parameterizations at every time step of a simulation. IM-UFF has been evaluated on a large set of benchmarks and is proposed as a self-contained implementation integrated in a new module for the SAMSON software platform for computational nanoscience available at http://www.samson-connect.net.     

Computational analysis of Asp519 and Glu665 mutations of coagulation factor FVIIIa: Implications for enhanced binding affinity of A2-domain

The A2-domain of blood coagulation factor VIIIa is non-covalently bound to the A1 and A3 domains via weak intermolecular interactions. Functional instability due to rapid dissociation of A2-domain from the active FVIII in blood presents a major hurdle for the therapeutic applications of FVIIIa to treat Hemophilia-A. To identify the ideal hot-spot residues at the interface of A2 and A1/A3 domains that could enhance the structural stability of FVIIIa, we performed a comprehensive computational mutagenesis study of two A2-domain residues, Asp519 and Glu665, that interface the A1 and A3-domains. Each residue was mutated to 15 uncharged amino-acids and the mutant structures were refined by MD simulations. Based on the estimated relative binding affinities of mutant structures, we predict that the mutation of Asp519 to Leu, Gln, Thr, Val and the mutation of Glu665 to Val, Ile, Met, Asn and Trp enhance the A2-domain binding affinity by more than 20 kcal/mol, compared to the WT structure. We anticipate that these predictions will be valuable for enzymatic studies towards the rational design of FVIIIa synthetic constructs with improved A2-domain binding affinity.     

The Ground Process Segment of SAR Altimeter

The key innovation technology of SAR Altimeter (Synthetic Aperture Radar Altimeter)are Doppler\|beam sharpen and delay/Doppler range compensation.The cooperation of these two technologies makes it has high along track resolution and high precision in height measurement.The ground processor is the key hinge to make sure that SAR altimeter could obtain these superiorities.Many key technologies for SAR altimeter processor,such as Doppler beam\|sharpen,delay/Doppler compensation and the second range correction,multilook,echo model and gradient function for retracker,are introduced in the paper.Based on the processor and related work,some simulation work and airborne experiment were tested by the processor,and both of the quantity results show that the SAR altimeter has more potential superiorities.     

Real-time approximation of molecular interaction interfaces based on hierarchical space decomposition

The interaction interface between two molecules can be represented as a bisector surface equidistant from the two sets of spheres of varying radii representing atoms. We recursively divide a box containing both sphere-sets into uniform pairs of sub-boxes. The distance from each new box to each sphere-set is conservatively approximated by an interval, and the number of sphere-box computations is greatly reduced by pre-partitioning each sphere-set using a kd-tree. The subdivision terminates at a specified resolution, creating a box partition (BP) tree. A piecewise linear approximation of the bisector surface is then obtained by traversing the leaves of the BP tree and connecting points equidistant from the sphere-sets. In 124 experiments with up to 16,728 spheres, a bisector surface with a resolution of 1/2⁴ of the original bounding box was obtained in 28.8 ms on average.