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...     

Water Pollution Threat to the Environment by a Urea Plant

Disposal of untreated industrial effluents is drastically deteriorating the quality of underground water. Research work has been conducted to analyze the effect of disposal of urea plant effluent on the quality of ground water of the District Mianwali Daudkhail, Pakistan. For this purpose the effluent and ground water samples were analyzed for pH, TDS, TSS, Cl, F, COD, BOD, Fe, Zn, Pb, Cu, Cr, Cd, Mn, and As. Results obtained were compared with WHO and NEQS standards for drinking and effluent emission limits, respectively. Moreover, effluent samples were also evaluated for irrigation purposes and results compared with criteria recommended for irrigation water. Results showed though the effluents were according to the standards given by National Environmental Quality Standards (NEQS) for liquid emission and fit for irrigation purposes, the quality of underground water was below standard due to having a higher quantity of total dissolved solids than permissible.     

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.     

Synthesis and protein degradation capacity of photoactivated enediynes

[structure: see text] The viability of proteins as targets of thermally and photoactivated enediynes has been confirmed at the molecular level. Model studies using a labeled substrate confirmed the efficacy of atom transfer from diyl radicals produced from enediynes to form captodatively stabilized carbon centered aminoacyl radicals, which then undergo either fragmentation or dimerization. To exploit this finding, a family of enediynes was developed using an intramolecular coupling strategy. Derivatives were prepared and used to target specific proteins, showing good correlation between affinity and photoinduced protein degrading activity. The findings have potential applications in the design of artificial chemical proteases and add to our understanding of the mechanism of action of the clinically important enediyne antitumor antibiotics.