Past, Present, and Future of Molecular Docking

The interface of any given ligand and protein—normally considered a macromolecule—of a known or predicted/modeled structure can be computed by determining each potential ligand position, resulting in an array of possibilities which are finally expressed in numerical energy values based on their thermodynamic affinity. Over the past few decades, this premier approach technique has proved to be crucial as an automated method in drug design and discovery, as well as in other fields. Data are retrieved from contour surface calculations for each ligand probe and can be analyzed to delineate regions of attraction on the basis of energy levels. Negative energy levels from contours are used to infer protein-ligand affinity clefts and are therefore relevant to drug design. Accordingly, molecular docking, framed as the “new microscope,” is part of a group of in silico computational techniques that enable the behavior of molecular chemistry to be analyzed and predicted in an inexpensive manner. From the starting point of framing the key terms in the binomial macromolecule-ligand docking approach, this chapter presents an introductory description of the progress made in this field of research over the past several years, in addition to present and future perspectives. This chapter presents a broad plethora of possibilities arising from the old docking alternatives to the current software technology and critically dissects and discusses the emerging trends. Despite the emergence of more degrees of freedom, a number of flexible conglomerates have not been well developed, and there are still computational limitations to solve, including several features in the focused technique. The present goals, such as molecular flexibility, binding entropy, and the presence of ions and solute conditions, are revisited with the purpose of anticipating the challenges, goals, and achievements in this field over the next few years or decades

Del consumo ocasional del tabaco a la adicción a la nicotina

Introduction. The occasional consumption of nicotine can generate a dependency or addiction, being detectable through changes in neurobiological mechanisms. Objective. Contextualize from consumption to addiction and theoretically identify the neurobiological mechanism of transition from regular tobacco use to nicotine addiction. Methodology. A search for articles in English and Spanish was carried out using different databases and combinations of keywords, articles that described the characteristics of the neurobiological processes involved in the use or intermittent consumption of tobacco and nicotine addiction were selected. as the main theme. Results. The number of investigations related to this topic is reduced, even more in relation to the description of the processes and neural changes of nicotine addiction. Drug addiction is a complex neurobehavioral process that alters thecircuits of the motivation-reward system of the brain, due to the decrease in dopamine and the affectation in the regulation of glutamate in the basal ganglia and extension of the amygdala is associated with the craving, anticipation, and deficits in executive function. Conclusions. Tobacco is considered a legal drug, so its consumption seems to be harmless. However, the evidence shows that its long-term consumption has serious consequences on the health of individuals. Understanding how occasional smoking changes to chronic use makes us more aware of adaptations in the brain.Introducción. El consumo ocasional de nicotina puede generar una dependencia o adicción, siendo detectable mediante modificaciones en los mecanismos neurobiológicos. Objetivo. Contextualizar del consumo a la adicción e identificar teóricamente el  mecanismo neurobiológico de transición del consumo regular del tabaco a la adicción de la nicotina. Metodología. Se realizó una búsqueda de artículos en inglés y español usando diferentes bases de datos y combinaciones de palabras clave, se seleccionaron los artículos que describieran las características de los procesos neurobiológicos implicados en el uso o consumo intermitentedel tabaco a la adicción a la nicotina como el tema principal. Resultados. El número de investigaciones relacionados a este tema es reducido, aún más en relación con la descripción de los procesos y cambios neurales de la adicción a la nicotina. La adicción a las drogas es un proceso neuroconductual complejo que altera los circuitos del sistema de motivaciónrecompensa del cerebro, por la disminución de la dopamina y la afectación en la regulación del glutamato en los ganglios basales y extensión de la amígdala se asocia con el craving, la anticipación y el déficit en la función ejecutiva. Conclusiones. El tabaco está considerado como una droga legal, por lo que su consumo pareciera ser inofensivo. Sin embargo, las evidencias muestran que su consumo a largo plazo tiene consecuencias graves en la salud de los individuos. El entender cómo cambia el hábito de fumar ocasionalmente al consumocrónico nos hace más conscientes sobre las adaptaciones en el cerebro

Influence of Drugs on Cognitive Functions

Disorders related to the misuse of certain drugs represent not only a worldwide public health problem, but also an economic and social issue. Adolescents and children represent the most vulnerable population for drug consumption and addiction. At this early stage in life, a crucial phase of the neurodevelopmental process, substance abuse can induce brain plasticity mechanisms that may produce long-lasting changes in neural circuitry and ultimately behavior. One of the consequences of these changes is the impairment of cognitive functions, with academic negative impact in the acquisition of new knowledge. In this chapter, we will describe the effects of illicit substances of abuse, both stimulants and depressants as well as prescription drug misuse and its influence of on learning and memory processes. Recent evidence on the new so-called smart drugs is also discussed

La comunicación de la ciencia en América Latina: esfuerzos de evaluación en la diversidad

Este libro presenta una compilación de 11 artículos que se inscriben en diferentes líneas temáticas dentro de la Comunicación de la ciencia, pero que tienen como hilo común la presentación de resultados de evaluación, en diferentes enfoques y niveles, y que son una breve muestra del quehacer en el campo.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Sociales::Centro de Investigación en Comunicación (CICOM

Seaweeds-derived compounds modulating effects on signal transduction pathways: A systematic review

Background Recently, the study of marine natural products has gained interest due to their relevant biological activities. Specially, seaweeds produce bioactive compounds that could act as modulators of cell signaling pathways involved in a plethora of diseases. Thereby, the description of the molecular mechanisms by which seaweeds elicit its biological functions will certainly pave the way to the pharmacological development of drugs. Aim This review describes the molecular mechanisms by which seaweeds act and its possible utilization in the design of new drugs. Methods This review was conducted according to the PRISMA-P guidelines for systematic reviews. Two independent authors searched into four different databases using combinations of keywords. Two more authors selected the articles following the eligibility criteria. Information extraction was conducted by two separated authors and entered into spreadsheets. Methodological quality and risk of bias were determined applying a 12-question Risk of Bias criteria tool. Results and discussion We found 2360 articles (SCOPUS: 998; PubMed: 678; Wiley: 645 and EBSCO: 39) using the established keywords, of which 113 articles fit the inclusion criteria and were included in the review. This work comprises studies in cell lines, and animal models, any clinical trial was excluded. The articles were published from 2005 up to March 31st 2018. The biggest amount of articles was published in 2017. Furthermore, the seaweeds tested in the studies were collected in 15 countries, mainly in Eastern countries. We found that the main modulated signaling pathways by seaweeds-derivate extracts and compounds were: L-Arginine/NO, TNF-α, MAPKs, PI3K/AKT/GSK, mTOR, NF-κB, extrinsic and intrinsic apoptosis, cell cycle, MMPs and Nrf2. Finally, the articles we analyzed showed moderate risk of bias in almost all the parameters evaluated. However, the studies fail to describe the place and characteristics of sample collection, the sample size, and the blindness of the experimental design. Conclusion In this review we identified and summarized relevant information related to seaweed-isolated compounds and extracts having biological activity; their role in different signal pathways to better understand their potential to further development of cures for cancer, diabetes, and inflammation-related diseases

Brown Seaweed Egregia menziesii’s Cytotoxic Activity against Brain Cancer Cell Lines

Brown seaweeds contain bioactive compounds that show anti-tumorigenic effects. These characteristics have been repeatedly observed in the Lessoniaceae family. Egregia menziesii, a member of this family, is distributed in the North Pacific and its properties have been barely studied. We evaluated herein the cytotoxic and anti-proliferative activity of extracts of this seaweed, through toxicity assay in Artemia salina and lymphocytes, and MTT proliferation assay, in Bergmann glia cells, 3T3-L1 and brain cancer cell lines. E. menziesii’s extracts inhibited the spread of all the tested cell lines. The hexane extract showed the highest cytotoxic activity, while the methanol extract was moderately cytotoxic. Interestingly, seaweed extracts displayed a selective inhibition pattern. These results suggest that E. menziesii’s extracts might be good candidates for cancer prevention and the development of novel chemotherapies due to its highest cytotoxicity in transformed cells compare to glia primary cultures