In silico screening of HIV-1 non-nucleoside reverse transcriptase and protease inhibitors

Two targets, reverse transcriptase (RT) and protease from HIV-1, were used during the past two decades to the discovery of non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) that belong to the arsenal of the antiretroviral therapy. Herein these enzymes were chosen as templates for conducting a computer-aided ligand design. Ligand and structure-based drug designs were the starting points to select compounds from a database bearing more than five million compounds by means of cheminformatic tools. New promising lead structures are retrieved from the database, which are open to acquisition and test. Classes of molecules already described as NNRTI or PI in the literature also came out and were useful to prove the reliability of the workflow, and thus validating the work carried out so far. (c) 2007 Elsevier Masson SAS. All rights reserved.

Package models and the information crisis of prebiotic evolution

The coexistence between different types of templates has been the choice solution to the information crisis of prebiotic evolution, triggered by the finding that a single RNA-like template cannot carry enough information to code for any useful replicase. In principle, confining d distinct templates of length L in a package or protocell, whose Survival depends on the coexistence of the templates it holds in, could resolve this crisis provided that d is made sufficiently large. Here we review the prototypical package model of Niesert et al. [1981. Origin of life between Scylla and Charybdis. J. Mol. Evol. 17, 348-353] which guarantees the greatest possible region of viability of the protocell population, and show that this model, and hence the entire package approach, does not resolve the information crisis. In particular, we show that the total information stored in a viable protocell (Ld) tends to a constant value that depends only on the spontaneous error rate per nucleotide of the template replication mechanism. As a result, an increase of d must be followed by a decrease of L, so that the net information gain is null. (C) 2008 Elsevier Ltd. All rights reserved.

Wavelet-based dynamic time warping

Dynamic Time Warping (DTW), a pattern matching technique traditionally used for restricted vocabulary speech recognition, is based on a temporal alignment of the input signal with the template models. The principal drawback of DTW is its high computational cost as the lengths of the signals increase. This paper shows extended results over our previously published conference paper, which introduces an optimized version of the DTW I hat is based on the Discrete Wavelet Transform (DWT). (C) 2008 Elsevier B.V. All rights reserved.

Statistical coupling analysis of aspartic proteinases based on crystal structures of the Trichoderma reesei enzyme and its complex with pepstatin A

The crystal structures of an aspartic proteinase from Trichoderma reesei (TrAsP) and of its complex with a competitive inhibitor, pepstatin A, were solved and refined to crystallographic R-factors of 17.9% (R(free)=21.2%) at 1.70 angstrom resolution and 15.81% (R(free) = 19.2%) at 1.85 angstrom resolution, respectively. The three-dimensional structure of TrAsP is similar to structures of other members of the pepsin-like family of aspartic proteinases. Each molecule is folded in a predominantly beta-sheet bilobal structure with the N-terminal and C-terminal domains of about the same size. Structural comparison of the native structure and the TrAsP-pepstatin complex reveals that the enzyme undergoes an induced-fit, rigid-body movement upon inhibitor binding, with the N-terminal and C-terminal lobes tightly enclosing the inhibitor. Upon recognition and binding of pepstatin A, amino acid residues of the enzyme active site form a number of short hydrogen bonds to the inhibitor that may play an important role in the mechanism of catalysis and inhibition. The structures of TrAsP were used as a template for performing statistical coupling analysis of the aspartic protease family. This approach permitted, for the first time, the identification of a network of structurally linked residues putatively mediating conformational changes relevant to the function of this family of enzymes. Statistical coupling analysis reveals coevolved continuous clusters of amino acid residues that extend from the active site into the hydrophobic cores of each of the two domains and include amino acid residues from the flap regions, highlighting the importance of these parts of the protein for its enzymatic activity. (C) 2008 Elsevier Ltd. All rights reserved.

An algorithm for automatic checking of exercises in a dynamic geometry system: iGeom

One of the key issues in e-learning environments is the possibility of creating and evaluating exercises. However, the lack of tools supporting the authoring and automatic checking of exercises for specifics topics (e.g., geometry) drastically reduces advantages in the use of e-learning environments on a larger scale, as usually happens in Brazil. This paper describes an algorithm, and a tool based on it, designed for the authoring and automatic checking of geometry exercises. The algorithm dynamically compares the distances between the geometric objects of the student`s solution and the template`s solution, provided by the author of the exercise. Each solution is a geometric construction which is considered a function receiving geometric objects (input) and returning other geometric objects (output). Thus, for a given problem, if we know one function (construction) that solves the problem, we can compare it to any other function to check whether they are equivalent or not. Two functions are equivalent if, and only if, they have the same output when the same input is applied. If the student`s solution is equivalent to the template`s solution, then we consider the student`s solution as a correct solution. Our software utility provides both authoring and checking tools to work directly on the Internet, together with learning management systems. These tools are implemented using the dynamic geometry software, iGeom, which has been used in a geometry course since 2004 and has a successful track record in the classroom. Empowered with these new features, iGeom simplifies teachers` tasks, solves non-trivial problems in student solutions and helps to increase student motivation by providing feedback in real time. (c) 2008 Elsevier Ltd. All rights reserved.

Elementary Petri net inside RFID distributed database (PNRD)

Usually, a Petri net is applied as an RFID model tool. This paper, otherwise, presents another approach to the Petri net concerning RFID systems. This approach, called elementary Petri net inside an RFID distributed database, or PNRD, is the first step to improve RFID and control systems integration, based on a formal data structure to identify and update the product state in real-time process execution, allowing automatic discovery of unexpected events during tag data capture. There are two main features in this approach: to use RFID tags as the object process expected database and last product state identification; and to apply Petri net analysis to automatically update the last product state registry during reader data capture. RFID reader data capture can be viewed, in Petri nets, as a direct analysis of locality for a specific transition that holds in a specific workflow. Following this direction, RFID readers storage Petri net control vector list related to each tag id is expected to be perceived. This paper presents PNRD cornerstones and a PNRD implementation example in software called DEMIS Distributed Environment in Manufacturing Information Systems.

Three-Dimensional Quantitative Structure-Activity Relationship Study of Antitumor 2-Formylpyridine Thiosemicarbazones Derivatives as Inhibitors of Ribonucleotide Reductase

In order to extend previous SAR and QSAR studies, 3D-QSAR analysis has been performed using CoMFA and CoMSIA approaches applied to a set of 39 alpha-(N)-heterocyclic carboxaldehydes thiosemicarbazones with their inhibitory activity values (IC(50)) evaluated against ribonucleotide reductase (RNR) of H.Ep.-2 cells (human epidermoid carcinoma), taken from selected literature. Both rigid and field alignment methods, taking the unsubstituted 2-formylpyridine thiosemicarbazone in its syn conformation as template, have been used to generate multiple predictive CoMFA and CoMSIA models derived from training sets and validated with the corresponding test sets. Acceptable predictive correlation coefficients (Q(cv)(2) from 0.360 to 0.609 for CoMFA and Q(cv)(2) from 0.394 to 0.580 for CoMSIA models) with high fitted correlation coefficients (r` from 0.881 to 0.981 for CoMFA and r(2) from 0.938 to 0.993 for CoMSIA models) and low standard errors (s from 0.135 to 0.383 for CoMFA and s from 0.098 to 0.240 for CoMSIA models) were obtained. More precise CoMFA and CoMSIA models have been derived considering the subset of thiosemicarbazones (TSC) substituted only at 5-position of the pyridine ring (n=22). Reasonable predictive correlation coefficients (Q(cv)(2) from 0.486 to 0.683 for CoMFA and Q(cv)(2) from 0.565 to 0.791 for CoMSIA models) with high fitted correlation coefficients (r(2) from 0.896 to 0.997 for CoMFA and r(2) from 0.991 to 0.998 for CoMSIA models) and very low standard errors (s from 0.040 to 0.179 for CoMFA and s from 0.029 to 0.068 for CoMSIA models) were obtained. The stability of each CoMFA and CoMSIA models was further assessed by performing bootstrapping analysis. For the two sets the generated CoMSIA models showed, in general, better statistics than the corresponding CoMFA models. The analysis of CoMFA and CoMSIA contour maps suggest that a hydrogen bond acceptor near the nitrogen of the pyridine ring can enhance inhibitory activity values. This observation agrees with literature data, which suggests that the nitrogen pyridine lone pairs can complex with the iron ion leading to species that inhibits RNR. The derived CoMFA and CoMSIA models contribute to understand the structural features of this class of TSC as antitumor agents in terms of steric, electrostatic, hydrophobic and hydrogen bond donor and hydrogen bond acceptor fields as well as to the rational design of this key enzyme inhibitors.

Structural and vibrational characterization of polyaniline nanofibers prepared from interfacial polymerization

This work deals with the structural and vibrational characterization of PANI nanofibers prepared through interfacial polymerization using different concentrations of HCl aqueous solution. The results were compared to those obtained by PANI prepared through the conventional route. X-ray diffraction and small-angle X-ray scattering techniques showed that high concentrations of HCl solutions used in the preparation of the PANI nanofibers reduce their crystallinity. The increase of regions with granular morphology was also observed in the scanning electron microscopy images. The changes in the resonance Raman spectra from 200 to 500 cm(-1), FTIR spectra, and the EPR data of the PANI nanofibers reveal an increase in the torsion angles of C-ring-N-C-ring segments owing the formation of bipolarons in the PANI backbone higher than the PANI samples prepared by conventional route.

Electrostatic layer-by-layer deposition and electrochemical characterization of thin films composed of MnO(2) nanoparticles in a room-temperature ionic liquid

Thin films of MnO(2) nanoparticles were grown using the layer-by-layer method with poly (diallyldimetylammonium) as the intercalated layer. The film growth was followed by UV-vis, electrochemical quartz crystal microbalance (EQCM), and atomic force microscopy. Linear growth due to electrostatic immobilization of layers was observed up to 30 bilayers, but electrical connectivity was maintained only for 12 MnO(2)/PPDA bilayers. The electrochemical characterization of this film in 1-butyl-2,3-dimethyl-imidazolium (BMMI) bis(trifluoromethanesulfonyl)imide (TFSI) (BMMITFSI) with and without addition of a lithium salt indicated a higher electrochemical response of the nanostructured electrode in the lithium-containing electrolyte. On the basis of EQCM experiments, it was possible to confirm that the charge compensation process is achieved mainly by the TFSI anion at short times (<2 s) and by BMMI and lithium cations at longer times. The fact that large ions like TFSI and BMMI participate in the electroneutrality is attributed to the redox reaction that occurs at the superficial sites and to the high concentration of these species compared to that of lithium cations.

Spectroscopic characterization of the structural changes of polyaniline nanofibers after heating

The thermal behavior of PANI nanofibers doped with beta-naphthalenesulfonic acid (beta-NSA) was investigated and their morphological and structural changes after heating were monitored by SEM, XRD and Raman techniques, respectively. By using electron-scanning microscopy it is possible to verify that the nanofiber morphology is stable and no polymer degradation is observed in thermogravimetric (TG) data up to 200 degrees C. Nevertheless, the heating promotes the formation of cross-linking structures (phenazine and/or oxazine-like rings), that is clearly demonstrated by the presence of bands at ca. 578, 1398, and 1644 cm(-1) in resonance Raman spectra of heated PANI-NSA samples. The most important consequence of the formation of cross-linking structures in PANI-NSA samples is that these samples retain their nanofiber morphology upon HCl doping in contrast to PANI-NSA nanofibers without heating. (c) 2007 Elsevier Ltd. All rights reserved.

Using Polycarbonate Membranes as Templates for the Preparation of Au Nanostructures for Surface-Enhanced Raman Scattering

Polycarbonate membranes (PCM) of various pores sizes (400, 200, 100 and 50 nm) were used as templates for gold deposition. The electrodeposition from gold ions resulted in the formation of gold nanotubes when large pores size PCMs (400 and 200 nm) were used. On the other hand, gold nanowires were predominant for the PCMs with smaller pores size (100 and 50 nm). Surface-enhanced Raman scattering (SERS) from the probe molecule 4-mercaptopyridine (4-MPy) was obtained from all these nanostructures. The SERS efficiency of the substrates produced using the PC M templates were compared to two commonly used SERS platforms: a roughened gold electrode and gold nanostructures electrodeposited through organized polystyrene spheres (PSS). The SERS signal of the probe molecule increased as the pore diameter of the PCM template decreased. Moreover, the SERS efficiency from the nanostructures produced using 50 nm PCM templates was four and two times better than the signal from the roughened gold electrode and the PSS template, respectively. The SERS substrates prepared using PCM templates were more homogenous over a larger area (ca. 1 cm(2)), presented better spatial and sample to sample reproducibility than the other substrates. These results show that SERS substrates prepared using PCM templates are promising for the fabrication of planar SERS platforms for analytical/bioanalytical applications.

The role of cross-linking structures to the formation of one-dimensional nano-organized polyaniline and their Raman fingerprint

In the present work. the resonance Raman. UV-vis-NIR and scanning electron microscopic (SEM) data of nanorods (about similar to 300 rim in diameter) and nanofibers (about similar to 93 nm in diameter) of PANI are presented and compared. The PANI samples were synthesized in aqueous media with dodecybenzenesulfonic acid (DBSA) and beta-naphtalenesulfonic acid (beta-NSA) as dopants, respectively. The presence of hands at 578, 1400 and 1632cm(-1) in the Raman spectra of PANI-NSA and PANI-DBSA shows that the formation of cross-linking structures is a general feature of the PANI chains prepared in micellar media. It is proposed that these structures are responsible for the one-dimensional PANI morphology formation. In addition, the Raman band at 609cm(-1) of PANI fibers is correlated with the extended PANI chain coil formation. (C) 2008 Elsevier B.V. All rights reserved.