QSAR model for alignment-free prediction of human breast cancer biomarkers based on electrostatic potentials of protein pseudofolding HP-lattice networks

Network theory allows relationships to be established between numerical parameters that describe the molecular structure of genes and proteins and their biological properties. These models can be considered as quantitative structure-activity relationships (QSAR) for biopolymers. The work described here concerns the first QSAR model for 122 proteins that are associated with human breast cancer (HBC), as identified experimentally by Sj?blom et al. (Science 2006, 314, 268) from over 10,000 human proteins. In this study, the 122 proteins related to HBC (HBCp) and a control group of 200 proteins that are not related to HBC (non-HBCp) were forced to fold in an HP lattice network. From these networks a series of electrostatic potential parameters (xi(k)) was calculated to describe each protein numerically. The use of xi(k) as an entry point to linear discriminant analysis led to a QSAR model to discriminate between HBCp and non-HBCp, and this model could help to predict the involvement of a certain gene and/or protein in HBC. In addition, validation procedures were carried out on the model and these included an external prediction series and evaluation of an additional series of 1000 non-HBCp. In all cases good levels of classification were obtained with values above 80%. This study represents the first example of a QSAR model for the computational chemistry inspired search of potential HBC protein biomarkers.     

Production and Characterization of Extracellular α-Amylase Produced by Wickerhamia sp. X-Fep

A yeast isolate able to produce high levels of extracellular ??-amylase was selected from a collection of 385 yeasts and identified as Wickerhamia sp. by the sequence of the D1/D2 domain of the 26?S rDNA gene. Part of the nucleotide sequence of the amy1-W gene was cloned, and a sequence of 191 amino acids deduced from this gene was analyzed. The peptide contains three characteristic well-conserved regions in the active sites of ??-amylases (EC 3.2.1.1). The enzyme was purified and in situ activity showed only one band with amylolytic activity. The molecular mass of the ??-amylase was estimated at 54?kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Enzymatic activity on soluble starch as substrate was optimal at pH 5?C6 and 50 °C. This thermostable enzyme was inhibited by EDTA?CNa₂ and 1,10-phenanthroline; the activity of the dialyzed enzyme was reactivated with Ca²⁺ and Mg²⁺ cations, which indicates that the ??-amylase is a metalloenzyme. ??-Amylase production was induced by starch and maltose and repressed by glucose. The high yield and productivity found in this work makes this Wickerhamia sp. strain a promising candidate for the biotechnological production of ??-amylase.     

Synthesis of glycolide/trimethylene carbonate copolymers: Influence of microstructure on properties

Copolymers of glycolide and trimethylene carbonate with different compositions and microstructures (i.e. random, blocky and segmented) were synthesized by two-step ring opening polymerization.NMR analyses revealed that transesterification reactions took place during the first step, which corresponded to the synthesis of soft segments, and mainly when the trimethylene carbonate content of the reaction medium was high. The transesterification percentage did not significantly change with the addition of hard blocks in the second reaction step. Infrared spectroscopy was a complementary, highly effective tool to evaluate the hard segment length, crystallinity and glycolide percentage incorporated into the crystalline phase for all studied samples.Calorimetric analyses showed dependency of properties on the length of the polyglycolide hard segment and also good miscibility between glycolide and trimethylene carbonate rich phases. Crystalline morphologies attained with segmented and random copolymers were significantly different, although in all cases a positive birefringence was detected.Thermogravimetric analyses indicated that all studied copolymers had a similar degradation behavior, which was intermediate between those observed in the corresponding homopolymers. Samples with a significant glycolide unit content showed a stabilizing effect for the degradation of poly(trimethylene carbonate) blocks.     

Computerized modeling of adenosine triphosphate, adenosine triarsenate and adenosine trivanadate

Computerized molecular models of adenosine triphosphate, adenosine tri-arsenate and adenosine trivanadate have been generated using the molecular mechanics technique. The analysis of structural parameters indicated that, at least theoretically, adenosine triarsenate is a realistic candidate for replacement of adenosine triphosphate in biochemical pathways. On the contrary, the structural arrangement of the inorganic segment of adenosine trivanadate does not seem to be capable of withstanding a swift hydrolytical splitting in aqueous milieu. It was shown that the universal force field as implemented in Gaussian software packages is an appropriate tool for the optimization of less-common bioactive compositions.     

Rheometry-PIV of shear-thickening wormlike micelles

The shear-thickening behavior of an equimolar semidilute aqueous solution of 40 mM/L cetylpyridinium chloride and sodium salicylate was studied in this work by using a combined method of rheometry and particle image velocimetry (PIV). Experiments were conducted at 27.5 degrees C with Couette, vane-bob, and capillary rheometers in order to explore a wide shear stress range as well as the effect of boundary conditions and time of flow on the creation and destruction of shear-induced structures (SIS). The use of the combined method of capillary rheometry with PIV allowed the detection of fast spatial and temporal variations in the flow kinematics, which are related to the shear-thickening behavior and the dynamics of the SIS but are not distinguished by pure rheometrical measurements. A rich-in-details flow curve was found for this solution, which includes five different regimes. Namely, at very low shear rates a Newtonian behavior was found, followed by a shear thinning one in the second regime. In the third, shear banding was observed, which served as a precursor of the SIS and shear-thickening. The fourth and fifth regimes in the flow curve were separated by a spurtlike behavior, and they clearly evidenced the existence of shear-thickening accompanied by stick-slip oscillations at the wall of the rheometer, which subsequently produced variations in the shear rate under shear stress controlled flow. Such a stick-slip phenomenon prevailed up to the highest shear stresses used in this work and was reflected in asymmetric velocity profiles with spatial and temporal variations linked to the dynamics of creation and breakage of the SIS. The presence of apparent slip at the wall of the rheometer provides an energy release mechanism which leads to breakage of the SIS, followed by their further reformation during the stick part of the cycles. In addition, PIV measurements allowed the detection of apparent slip at the wall, as well as mechanical failures in the bulk of the fluid, which suggests an extra contribution of the shear stress field to the SIS dynamics. Increasing the residence time of the fluid in the flow system enhanced the shear-thickening behavior. Finally, the flow kinematics is described in detail and the true flow curve is obtained, which only partially fits into the scheme of existing theoretical models for shear-thickening solutions.     

Interaction between the conjugated polyelectrolyte poly{1,4-phenylene[9,9-bis(4-phenoxybutylsulfonate)]fluorene-2,7-diyl} copolymer and the lecithin mimic 1-O-(l-Arginyl)-2,3-O-dilauroyl-sn-glycerol in aqueous solution

In this paper, the interaction between the water-soluble conjugated polyelectrolyte poly{1,4-phenylene[9,9-bis(4-phenoxybutylsulfonate)]fluorene-2,7-diyl} copolymer and the amino acid glyceride conjugate 1-O-(L-arginyl)-2,3-O-dilauroyl-sn-glycerol dichlorohydrate (a mimic for the phospholipid lecithin) has been studied in aqueous solution by electronic spectroscopy (absorption and fluorescence) and small-angle neutron scattering (SANS). A significant increase in the polymer fluorescence and blue shift in its emission are observed on association with the surfactant. This is suggested to be due to breakup of polymer aggregates. In addition, the spectroscopic and photophysical data suggest this is followed by the vesicle to ribbon transition characteristic of this surfactant, leading to incorporation of single chains of the polymer within mixed polymer-surfactant aggregates. Support for this comes from preliminary SANS measurements, from which evidence for polymer dissolution and formation of two-dimensional structures has been obtained.     

Transport properties of the ionic liquid 1-ethyl-3-methylimidazolium chloride from equilibrium molecular dynamics simulation. The effect of temperature

We present here equilibrium molecular dynamics simulation results for self-diffusion coefficients, shear viscosity, and electrical conductivity in a model ionic liquid (1-ethyl-3-methylimidazolium chloride) at different temperatures. The Green-Kubo relations were employed to evaluate the transport coefficients. When compared with available experimental data, the model underestimates the conductivity and self-diffusion, whereas the viscosity is overpredicted, showing only a semiquantitative agreement with experimental data. These discrepancies are explained on the basis of the rigidity and lack of polarizability of the model. Despite this, the experimental trends with temperature are remarkably well reproduced, with a good agreement on the activation energies when available. No significant deviations from the Nernst-Einstein relation can be assessed on the basis of the statistical uncertainty of the simulations, although the comparison between the electric current and the velocity autocorrelation functions suggests some degree of cross-correlation among ions in a short time scale. The simulations reproduce remarkably well the slope of the Walden plots obtained from experimental data of 1-ethyl-3-methylimidazolium chloride, confirming that temperature does not alter appreciably the extent of ion pairing.     

Perfect wetting along a three-phase line: theory and molecular dynamics simulations

Wetting behavior along a three-phase equilibrium has been obtained by density gradient theory (DGT) and molecular dynamics simulations for a type-II equal size Lennard-Jones mixture. In order to perform a consistent comparison between both methodologies, the molecular parameters of this type of mixture were defined from the global phase diagram of equal size Lennard-Jones mixtures. We have found excellent agreement between predictions from the DGT (coupled to a Lennard-Jones equation for the bulk phases) and simulations results for both the phase and interface behavior, in the whole temperature, pressure, and concentration ranges. For all conditions explored in this work, this type-II mixture shows a three-phase equilibrium composed by a bulk immiscible liquid phase (L1) and a bulk gas phase (G) separated by a second immiscible liquid phase (L2). A similar phase distribution is obtained from the interfacial concentration profile in the whole range of conditions used in this work. This type of structure is a clear evidence that L2 completely wets the GL1 interface. The wetting behavior is also confirmed by the values and evolution of the interfacial tensions. In summary, this kind of type-II mixture does not show wetting transitions and exhibits a permanent perfect wetting in all the thermodynamic conditions explored here.     

Screening of Food Grade Lipases to be Used in Esterification and Interesterification Reactions of Industrial Interest

Seven food grade commercially available lipases were immobilized by covalent binding on polysiloxane–polyvinyl alcohol (POS-PVA) hybrid composite and screened to mediate reactions of industrial interest. The synthesis of butyl butyrate and the interesterification of tripalmitin with triolein were chosen as model reactions. The highest esterification activity (240.63 μM/g min) was achieved by Candida rugosa lipase, while the highest interesterification yield (31%, in 72 h) was achieved by lipase from Rhizopus oryzae, with the production of about 15 mM of the triglycerides C₅₀ and C₅₂. This lipase also showed a good performance in butyl butyrate synthesis, with an esterification activity of 171.14 μM/g min. The results demonstrated the feasibility of using lipases from C. rugosa for esterification and R. oryzae lipase for both esterification and interesterification reactions.