IDSite: An accurate approach to predict P450-mediated drug metabolism

Accurate prediction of drug metabolism is crucial for drug design. Since a large majority of drugs metabolism involves P450 enzymes, we herein describe a computational approach, IDSite, to predict P450-mediated drug metabolism. To model induced-fit effects, IDSite samples the conformational space with flexible docking in Glide followed by two refinement stages using the Protein Local Optimization Program (PLOP). Sites of metabolism (SOMs) are predicted according to a physical-based score that evaluates the potential of atoms to react with the catalytic iron center. As a preliminary test, we present in this paper the prediction of hydroxylation and O-dealkylation sites mediated by CYP2D6 using two different models: a physical-based simulation model, and a modification of this model in which a small number of parameters are fit to a training set. Without fitting any parameters to experimental data, the Physical IDSite scoring recovers 83% of the experimental observations for 56 compounds with a very low false positive rate. With only 4 fitted parameters, the Fitted IDSite was trained with the subset of 36 compounds and successfully applied to the other 20 compounds, recovering 94% of the experimental observations with high sensitivity and specificity for both sets.     

Dynamics of pistachio oils by proton nuclear magnetic resonance relaxation dispersion

A number of pistachio oils were selected in order to test the efficacy of nuclear magnetic resonance relaxation dispersion (NMRD) technique in the evaluation of differences among oils (1) obtained from seeds subjected to different thermal desiccation processes, (2) retrieved from seeds belonging to the same cultivar grown in different geographical areas and (3) produced by using seed cultivars sampled in the same geographical region. NMRD measures relaxation rate values which are related to the dynamics of the chemical components of complex food systems. Results not only allowed to relate kinematic viscosity to relaxometry parameters but also were successful in the differentiation among the aforementioned oils. In fact, from the one hand, the larger the kinematic viscosity, the faster the rotational motions appeared as compared to the translational ones. On the other hand, relaxation rate curves (NMRD) varied according to the oxidative stresses and chemical composition of each sample. The present study showed for the first time that NMRD is a very promising technique for quick evaluations of pistachio oil quality without the need for time-consuming chemical manipulations.     

Bilinear optimality constraints for the cone of positive polynomials

For a proper cone \({{\mathcal K}\subset\mathbb{R}^n}\) and its dual cone \({{\mathcal K}^*}\) the complementary slackness condition \({\langle{\rm {\bf x}},{\rm {\bf s}}\rangle=0}\) defines an n-dimensional manifold \({C({\mathcal K})}\) in the space \({{\mathbb R}^{2n}}\) . When \({{\mathcal K}}\) is a symmetric cone, points in \({C({\mathcal K})}\) must satisfy at least n linearly independent bilinear identities. This fact proves to be useful when optimizing over such cones, therefore it is natural to look for similar bilinear relations for non-symmetric cones. In this paper we define the bilinearity rank of a cone, which is the number of linearly independent bilinear identities valid for points in \({C({\mathcal K})}\) . We examine several well-known cones, in particular the cone of positive polynomials \({{\mathcal P}_{2n+1}}\) and its dual, and show that there are exactly four linearly independent bilinear identities which hold for all \({({\rm {\bf x}},{\rm {\bf s}})\in C({\mathcal P}_{2n+1})}\), regardless of the dimension of the cones. For nonnegative polynomials over an interval or half-line there are only two linearly independent bilinear identities. These results are extended to trigonometric and exponential polynomials. We prove similar results for Müntz polynomials.     

Antimicrobial graphene polymer (PVK-GO) nanocomposite films

The first report on the fabrication and application of a nanocomposite containing poly-N-vinyl carbazole (PVK) polymer and graphene oxide (GO) as an antimicrobial film was demonstrated. The antimicrobial film was 90% more effective in preventing bacterial colonization relative to the unmodified surface. More importantly, the nanocomposite thin film showed higher bacterial toxicity than pure GO-modified surface.     

Dynamics of a hybrid vibro-impact oscillator: canonical formalism

Nonlinear Dynamics - Hybrid vibro-impact (HVI) oscillations is a strongly nonlinear dynamical regime that involves both linear oscillations and collisions under periodic, impulsive, or stochastic...     

Antibacterial Activity of Dental Composite with Ciprofloxacin Loaded Silver Nanoparticles

Resin composites have been widely used in dental restoration. However, polymerization shrinkage and resultant bacterial microleakage are major limitations that may lead to secondary caries. To overcome this, a new type of antibacterial resin composite containing ciprofloxacin-loaded silver nanoparticles (CIP-AgNPs) were synthesized. The chemical reduction approach successfully produced CIP-AgNPs, as demonstrated by FTIR, zeta potential, scanning electron microscopy, and ultraviolet-visible (UV-vis) spectroscopy. CIP-AgNPs were added to resin composites and the antibacterial activity of the dental composite discs were realized against Enterococcus faecalis, Streptococcus mutans, and the Saliva microcosm. The biocompatibility of modified resin composites was assessed and mechanical testing of modified dental composites was also performed. The results indicated that the antibacterial activity and compressive strength of resin composites containing CIP-AgNPs were enhanced compared to the control group. They were also biocompatible when compared to resin composites containing AgNPs. In short, these results established strong ground application for CIP-AgNP-modified dental composite resins.     

Synthesis of Starch-Grafted Polymethyl Methacrylate via Free Radical Polymerization Reaction and Its Application for the Uptake of Methylene Blue

In this research, a new biodegradable and eco-friendly adsorbent, starch-grafted polymethyl methacrylate (St-g-PMMA) was synthesized. The St-g-PMMA was synthesized by a free radical polymerization reaction in which methyl methacrylate (MMA) was grafted onto a starch polymer chain. The reaction was performed in water in the presence of a potassium persulfate (KPS) initiator. The structure and different properties of the St-g-PMMA was explored by FT-IR, 1H NMR, TGA, SEM and XRD. After characterization, the St-g-PMMA was used for the removal of MB dye. Different adsorption parameters, such as effect of adsorbent dose, effect of pH, effect of initial concentration of dye solution, effect of contact time and comparative adsorption study were investigated. The St-g-PMMA showed a maximum removal percentage (R%) of 97% towards MB. The other parameters, such as the isothermal and kinetic models, were fitted to the experimental data. The results showed that the Langmuir adsorption and pseudo second order kinetic models were best fitted to experimental data with a regression coefficient of R² = 0.93 and 0.99, respectively.     

Highly efficient triplet chain isomerization of Dewar benzenes: adiabatic rate constants from cage kinetics

Quantum yields as high as 120 were achieved for triplet-sensitized photoisomerizations of several Dewar benzene reactants, R, to the corresponding benzene products, P. Considerable chain amplification is maintained even at high conversion. All relevant rate constants of this triplet chain reaction were extracted from laser flash photolysis plus steady-state photolysis experiments. The crucial rate constant ka for adiabatic isomerization of the triplet reactant to triplet product (R* --> P*) cannot be directly measured because it is so large relative to the bimolecular rate of R* formation via sensitization. However, ka was obtained indirectly using a cage/encounter complex model to analyze the competition between the dissociation of encounter pairs with the sensitizer, e.g., S/R* --> S + R*, and the in-cage processes, S/R* --> S/P* --> S*/P, in nonviscous and viscous solvents. These measurements yielded ka values of (approximately 4-9) x 10(9) s(-1), which suggests that only a small (approximately 3 kcal/mol) energy barrier exists along the potential energy surface from R* to P*. Steady-state data indicated that the chain-terminating rate constant R* --> R is negligibly small, an ideal condition for chain amplification. Triplet energy transfer from a series of sensitizers to the Dewar benzene derivatives shows a nonclassical falloff in rate constants with decreasing sensitizer triplet energy, suggesting energy transfer to thermally distorted configurations having lower singlet-triplet energy gaps. As a result of distorted geometries of R* and P*, the chain-propagating energy transfer from P* to R proceeds with a rate constant of only approximately 2 x 10(7) M(-1) s(-1), despite strong exothermicity. The isomerization reaction can release over 100 kcal/kcal of absorbed photons due to the high-energy content of the reactant together with the large chain length.     

Addendum to “Unstable crack motion is predictable” [2005. JMPS 53, 1071]

Using a scaling relationship discussed in an earlier paper [Abraham, F. F., 2005. Unstable crack motion is predictable. J. Mech. Phys. Solids 53, 1071-1075], we find that the steady-state speed of a unidirectional crack moving in a hyperelastic solid equals the crack speed in a linear solid with our “effective spring constant”.     

Monte Carlo simulation using the Fourier transform of the interatomic potential

When doing Monte Carlo simulations using continuous potentials, the evaluation of the configurational potential energy ink-space by Fourier transformation is shown to be a computationally attractive scheme for systems where the long-range interatomic interaction spans a dimension comparable to the size of the simulated system.