Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors

Reverse transcriptase (RT) is a multifunctional enzyme in the human immunodeficiency virus (HIV)-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs) and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted.

Synthesis, characterization and computational studies of (E)-2-{[(2-aminopyridin-3-yl)imino]-methyl}-4,6-di-tert-butylphenol

(E)-2-{[(2-Aminopyridin-3-yl)imino]-methyl}-4,6-di-tert-butyl-phenol ( 3: ), a ligand containing an intramolecular hydrogen bond, was prepared according to a previous literature report, with modifications, and was characterized by UV-vis, FTIR, ¹H-NMR, 13C-NMR, HHCOSY, TOCSY and cyclic voltammetry. Computational analyses at the level of DFT and TD-DFT were performed to study its electronic and molecular structures. The results of these analyses elucidated the behaviors of the UV-vis and electrochemical data. Analysis of the transitions in the computed spectrum showed that the most important band is primarily composed of a HOMO→LUMO transition, designated as an intraligand (IL) charge transfer.

Computational modeling for irrigated agriculture planning. Part II: risk analysis

Techniques of evaluation of risks coming from inherent uncertainties to the agricultural activity should accompany planning studies. The risk analysis should be carried out by risk simulation using techniques as the Monte Carlo method. This study was carried out to develop a computer program so-called P-RISCO for the application of risky simulations on linear programming models, to apply to a case study, as well to test the results comparatively to the @RISK program. In the risk analysis it was observed that the average of the output variable total net present value, U, was considerably lower than the maximum U value obtained from the linear programming model. It was also verified that the enterprise will be front to expressive risk of shortage of water in the month of April, what doesn't happen for the cropping pattern obtained by the minimization of the irrigation requirement in the months of April in the four years. The scenario analysis indicated that the sale price of the passion fruit crop exercises expressive influence on the financial performance of the enterprise. In the comparative analysis it was verified the equivalence of P-RISCO and @RISK programs in the execution of the risk simulation for the considered scenario.

Warning system based on theoretical-experimental study of dispersion of soluble pollutants in rivers

Information about capacity of transport and dispersion of soluble pollutants in natural streams are important in the management of water resources, especially in planning preventive measures to minimize the problems caused by accidental or intentional waste, in public health and economic activities that depend on the use of water. Considering this importance, this study aimed to develop a warning system for rivers, based on experimental techniques using tracers and analytical equations of one-dimensional transport of soluble pollutants conservative, to subsidizing the decision-making in the management of water resources. The system was development in JAVA programming language and MySQL database can predict the travel time of pollutants clouds from a point of eviction and graphically displays the temporal distribution of concentrations of passage clouds, in a particular location, downstream from the point of its launch.

The Shadow Moiré method using the phase shifting technique and digital image processing: computational implementation and application to the 3D-reconstruction of a buckled plate

The Shadow Moiré fringe patterns are level lines of equal depth generated by interference between a master grid and its shadow projected on the surface. In simplistic approach, the minimum error is about the order of the master grid pitch, that is, always larger than 0,1 mm, resulting in an experimental technique of low precision. The use of a phase shift increases the accuracy of the Shadow Moiré technique. The current work uses the phase shifting method to determine the surfaces three-dimensional shape using isothamic fringe patterns and digital image processing. The current study presents the method and applies it to images obtained by simulation for error evaluation, as well as to a buckled plate, obtaining excellent results. The method hands itself particularly useful to decrease the errors in the interpretation of the Moiré fringes that can adversely affect the calculations of displacements in pieces containing many concave and convex regions in relatively small areas.

Learning about brain physiology and complexity from the study of the epilepsies

The brain is a complex system, which produces emergent properties such as those associated with activity-dependent plasticity in processes of learning and memory. Therefore, understanding the integrated structures and functions of the brain is well beyond the scope of either superficial or extremely reductionistic approaches. Although a combination of zoom-in and zoom-out strategies is desirable when the brain is studied, constructing the appropriate interfaces to connect all levels of analysis is one of the most difficult challenges of contemporary neuroscience. Is it possible to build appropriate models of brain function and dysfunctions with computational tools? Among the best-known brain dysfunctions, epilepsies are neurological syndromes that reach a variety of networks, from widespread anatomical brain circuits to local molecular environments. One logical question would be: are those complex brain networks always producing maladaptive emergent properties compatible with epileptogenic substrates? The present review will deal with this question and will try to answer it by illustrating several points from the literature and from our laboratory data, with examples at the behavioral, electrophysiological, cellular and molecular levels. We conclude that, because the brain is a complex system compatible with the production of emergent properties, including plasticity, its functions should be approached using an integrated view. Concepts such as brain networks, graphics theory, neuroinformatics, and e-neuroscience are discussed as new transdisciplinary approaches dealing with the continuous growth of information about brain physiology and its dysfunctions. The epilepsies are discussed as neurobiological models of complex systems displaying maladaptive plasticity.

Computational fluid dynamics evaluation of liquid food thermal process in a brick shaped package

Food processes must ensure safety and high-quality products for a growing demand consumer creating the need for better knowledge of its unit operations. The Computational Fluid Dynamics (CFD) has been widely used for better understanding the food thermal processes, and it is one of the safest and most frequently used methods for food preservation. However, there is no single study in the literature describing thermal process of liquid foods in a brick shaped package. The present study evaluated such process and the influence of its orientation on the process lethality. It demonstrated the potential of using CFD to evaluate thermal processes of liquid foods and the importance of rheological characterization and convection in thermal processing of liquid foods. It also showed that packaging orientation does not result in different sterilization values during thermal process of the evaluated fluids in the brick shaped package.