Study of the Differential Activity of Thrombin Inhibitors Using Docking, QSAR, Molecular Dynamics, and MM-GBSA

Indexación: Web of Science; Scopus.Non-peptidic thrombin inhibitors (TIs; 177 compounds) with diverse groups at motifs P1 (such as oxyguanidine, amidinohydrazone, amidine, amidinopiperidine), P2 (such as cyano-fluorophenylacetamide, 2-(2-chloro-6-fluorophenyl)acetamide), and P3 (such as phenylethyl, arylsulfonate groups) were studied using molecular modeling to analyze their interactions with S1, S2, and S3 subsites of the thrombin binding site. Firstly, a protocol combining docking and three dimensional quantitative structure-activity relationship was performed. We described the orientations and preferred active conformations of the studied inhibitors, and derived a predictive CoMSIA model including steric, donor hydrogen bond, and acceptor hydrogen bond fields. Secondly, the dynamic behaviors of some selected TIs (compounds 26, 133, 147, 149, 162, and 177 in this manuscript) that contain different molecular features and different activities were analyzed by creating the solvated models and using molecular dynamics (MD) simulations.We used the conformational structures derived from MD to accomplish binding free energetic calculations using MM-GBSA. With this analysis, we theorized about the effect of van der Waals contacts, electrostatic interactions and solvation in the potency of TIs. In general, the contents reported in this article help to understand the physical and chemical characteristics of thrombin-inhibitor complexes. © 2015 Mena-Ulecia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.014277

Análisis de la capacidad de soporte sísmica de fundaciones superficiales

Indexación: Web of Science; Scielo.In the context of engineering practice, the problem of the seismic bearing capacity of shallow foundations has been solved indirectly, either due an increase of the static allowable soil pressures related to the probability of occurrence of the design earthquake or by adopting an equivalent pseudo-static approach. However, during last decades, a series of analytical methods that directly address the problem from the seismic point of view has been developed. This paper presents a parametric comparative analysis of different methods for estimating seismic bearing capacity of shallow strip foundations. Analytical methods, developed in the framework of both limit equilibrium and limit analysis theories, and also simplified design procedures typically used in practice were considered. The results obtained show an important decrease of the bearing foundation capacity with increasing of the maximum earthquake acceleration, which highlights the need to obtain a measure of the reliability associated with both calculation methods and safety factors commonly used for seismic design.En el contexto de la práctica ingenieril, el problema de la capacidad de soporte sísmica de fundaciones superficiales generalmente ha sido resuelto, de modo indirecto, ya sea considerando un incremento en las tensiones admisibles estáticas del suelo, asociado a la probabilidad de ocurrencia de un cierto evento sísmico de diseño, o bien adoptando un enfoque de tipo pseudoestático equivalente. Sin embargo, durante las últimas décadas se han desarrollado una serie de métodos analíticos que abordan directamente el problema desde el punto de vista sísmico. Este artículo presenta un análisis comparativo de tipo paramétrico entre diferentes métodos para estimar la capacidad de soporte sísmica de fundaciones superficiales corridas. Se consideraron métodos analíticos, desarrollados en el contexto de las teorías de equilibrio límite y análisis límite, y también procedimientos de diseño simplificados típicamente utilizados en la práctica. Los resultados obtenidos muestran un importante deterioro de la capacidad de soporte de la fundación en la medida que la aceleración máxima del sismo aumenta, lo cual pone de manifiesto la necesidad de establecer una medida de la confiabilidad asociada a los métodos de cálculo y factores de seguridad comúnmente usados para diseño sísmico.http://ref.scielo.org/kp4j8

Theoretical design of stable small aluminium-magnesium binary clusters

We explore in detail the potential energy surfaces of the AlxMgy (x, y = 1–4) systems as case studies to test the utility and limitations of simple rules based on electron counts and the phenomenological shell model (PSM) for bimetallic clusters. We find that it is feasible to design stable structures that are members of this set of small Al–Mg binary clusters, using simple electron count rules, including the classical 4n + 2 Hückel model, and the most recently proposed PSM. The thermodynamic stability of the title compounds has been evaluated using several different descriptors, including the fragmentation energies and the electronic structure of the systems. Three stable systems emerge from the analysis: the Al4Mg, Al2Mg2 and Al4Mg4 clusters. The relative stability of Al4Mg is explained by the stability of the Al42− subunit to which the Mg atom donates its electrons. Here the Mg2+ sits above the aromatic 10 π-electron Al42− planar ring. The Al2Mg2 and Al4Mg4 clusters present more complicated 3D structures, and their stabilities are rationalized as a consequence of their closed shell nature in the PSM, with 10 and 20 itinerant electrons, respectively

Photo-absorption spectra of small hydrogenated silicon clusters using the time-dependent density functional theory

We present a systematic study of the photo-absorption spectra of various Si$_{n}$H$_{m}$ clusters (n=1-10, m=1-14) using the time-dependent density functional theory (TDDFT). The method uses a real-time, real-space implementation of TDDFT involving full propagation of the time dependent Kohn-Sham equations. Our results for SiH$_{4}$ and Si$_{2}$H$_{6}$ show good agreement with the earlier calculations and experimental data. We find that for small clusters (n<7) the photo-absorption spectrum is atomic-like while for the larger clusters it shows bulk-like behaviour. We study the photo-absorption spectra of silicon clusters as a function of hydrogenation. For single hydrogenation, we find that in general, the absorption optical gap decreases and as the number of silicon atoms increase the effect of a single hydrogen atom on the optical gap diminishes. For further hydrogenation the optical gap increases and for the fully hydrogenated clusters the optical gap is larger compared to corresponding pure silicon clusters.Comment: 6 pages, 5 figure

Quercetin Affects Erythropoiesis and Heart Mitochondrial Function in Mice

Copyright © 2015 Lina M. Ruiz et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Quercetin, a dietary flavonoid used as a food supplement, showed powerful antioxidant effects in different cellular models. However, recent in vitro and in vivo studies in mammals have suggested a prooxidant effect of quercetin and described an interaction with mitochondria causing an increase in O2 (∙-) production, a decrease in ATP levels, and impairment of respiratory chain in liver tissue. Therefore, because of its dual actions, we studied the effect of quercetin in vivo to analyze heart mitochondrial function and erythropoiesis. Mice were injected with 50 mg/kg of quercetin for 15 days. Treatment with quercetin decreased body weight, serum insulin, and ceruloplasmin levels as compared with untreated mice. Along with an impaired antioxidant capacity in plasma, quercetin-treated mice showed a significant delay on erythropoiesis progression. Heart mitochondrial function was also impaired displaying more protein oxidation and less activity for IV, respectively, than no-treated mice. In addition, a significant reduction in the protein expression levels of Mitofusin 2 and Voltage-Dependent Anion Carrier was observed. All these results suggest that quercetin affects erythropoiesis and mitochondrial function and then its potential use as a dietary supplement should be reexamined.Peer reviewe

Aproximación alanálisis de lavaloración de la prueba usando modified wigmorean analysis (MWA)

The present work shows how the analysis of the valuation of the proof, using tools of plot diagramming, can help the juridical operators to evaluate the quality of the argumentation of the juridical reasoning. There is applied the Modified Wigmorean Analysis (MWA) to a penal hypothetical case and to a real case, testing the process of analysis and diagramming and proving his utility. The conclusion outlines the advantages and weaknesses of the analysis and suggests adjustments to the process of diagramming

Beneficio que tiene la actividad física en alumnos de Diplomado en Habilidades Laborales de la Universidad Andrés Bello Casona Las Condes

Tesis (Profesor de Educación Física para la Enseñanza Básica, Licenciado en Educación)El presente estudio tiene por objetivo presentar los beneficios que obtienen a través de la actividad física los estudiantes del Diploma en Habilidades Laborales (DHL) por medio del planteamiento de objetivos que definen y caracterizan los fines de la investigación, en donde la importancia del estudio radica en la percepción que tienen los estudiantes con respecto los beneficios socioafectivos, académicos y físicos de la práctica de la actividad física. Cada objetivo se relaciona directamente con las preguntas abiertas que se realizan en la entrevista y en ella se manifiestan respuestas que logran resaltar la importancia que tiene la actividad física pero también la importancia que le brinda cada estudiante, demostrando cómo la actividad física forma parte de sus vidas, la motivación y entretención que les generan los talleres deportivos que son parte de la Dirección General de Desarrollo Estudiantil (DGDE) de la Universidad Andrés Bello

Estudio teórico de la evolución estructural y energética de los sistemas Si5-n(AlnHn)2- (n=0-5)

53 p.La nanotecnología comprende el estudio, diseño y creación de nuevos materiales a través del control de la materia a nivel de nanoescala. Un ejemplo de estos avances tecnológicos, es la elaboración de biochips para detectar proteínas, una metodología basada en inmovilizar y orientar proteínas sobre la superficie de zagregados atómicos preparados por medios físicos.Los clústeres atómicos se definen como cúmulos o agregados de átomos de tamaño intermedio entre el nivel molecular y el bulk de un sólido. Comprendiendo la estabilidad y enlace químico de estos sistemas, es posible en un futuro predecir y comprender de manera más adecuada los sitios de unión de algunas proteínas sobre estos agregados. La naturaleza química y física de los agregados atómicos puede ser descrita mediante el uso de métodos de la mecánica cuántica.Dentro del estudio químico y físico de los agregados atómicos, el estudio de la isovalencia es un área abierta y necesaria para comprender la estabilidad de estos sistemas. Un ejemplo de estos estudios, es la relación que existe entre los compuestos NaSi5 - y Si5 2- con B5H5 2- y NaB5H5 -, respectivamente, donde cada átomo de Si se comporta de la misma manera que una unidad BH. En esta investigación, se explora la isovalencia y la química que existe en clústeres atómicos conformados por átomos pertenecientes al grupo 13 y 14 de la tabla periódica. Concretamente, se estudia la evolución estructural del enlace químico en la transformación del clúster Si5 2- al Al5H5 2- , al intercambiar sucesivamentex un átomo de silicio por una unidad AlH. Utilizando el análisis de los Orbitales Naturales de Enlace (NBO), en conjunto con el análisis de enlace químico basado en el particionamiento de la densidad electrónica (AdNDP), la Función de Localización Electrónica (ELF) y los Orbitales Moleculares, se obtiene que la estructura tridimensional de los sistemas al realizar la transformación se conserva, y que los patrones de enlace, son acordes con los de los sistemas Si5-n(BnHn)2-(n = 0-5). 7 5. /ABSTRACT: Rol at the nanoscale level. An example of these technological advances is the development of biochips for detecting proteins, a methodology based on immobilize and guide proteins on the surface of atomic aggregates prepared by physical means. Atomic clusters are defined as aggregates of atoms of intermediate size between the molecular level and the bulk of a solid. Understanding the stability and chemical bonding of these systems will enable in the future, the prediction and proper understanding of the binding sites of some proteins on these aggregates. The chemical and physical nature of atomic clusters can be described using quantum mechanics methods. Within the chemical and physical study of atomic clusters, the study of isovalence is an open area and necessary to understand the stability of these systems. An example of these studies is the existing relationship between the NaSi5 - and Si5 2- with the NaB5H5 - and B5H5 2- compounds, respectively, where each Si atom behaves the same way as a unit of B-H. In this research, we explore the isovalence and the existing chemistry in atomic clusters built by atoms from the 13 and 14 group of the periodic table, especially compounds of B- and C as well as Al- and Si, which have the same number of valence electrons. Specifically, we study the structural evolution of the chemical bond in the transformation from the Si5 2- to the Al5H5 2- cluster by exchanging a silicon atom by an Al-H unit. Analysis using Natural Bond Orbital (NBO), chemical bond based on the partitioning of the electron density (AdNDP), the Electronics Location Function (ELF) and the Molecular Orbitals, indicate that the three-dimensional structure of the systems when performed the transformation is preserved, and that the bond patterns are consistent with the systems Si5-n (BnHn)2- (n = 0-5)