Molecular Dynamics Simulations of Substrate Release from Trypanosoma cruzi UDP-Galactopyranose Mutase

The enzyme UDP-galactopyranose mutase (UGM) represents a promising drug target for the treatment of infections with Trypanosoma cruzi. We have computed the Potential of Mean Force for the release of UDP-galactopyranose from UGM, using Umbrella Sampling simulations. The simulations revealed the conformational changes that both substrate and enzyme undergo during the process. It was determined that the galactopyranose portion of the substrate is highly mobile and that the opening/closing of the active site occurs in stages. Previously uncharacterized interactions with highly conserved residues were also identified. These findings provide new pieces of information that contribute to the rational design of drugs against T. cruzi.Fil: Cossio Pérez, Rodrigo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pierdominici Sottile, Gustavo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sobrado, Pablo. No especifíca;Fil: Palma, Juliana Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentin

Uso del conocimiento científico de estudiantes de pregrado de educación diferencial

The objectives of the study were to describe the scientific knowledge of undergraduate students of differential education and to compare with other national studies. We studied 79 students of differential education from a University of Santiago (Chile). Seventy-nine (02 male and 77 female) undergraduate students were selected in a non-probabilistic (intentional) manner in 2017 of the differential education ca- reer at the Universidad Católica Silva Henriquez (UCSH) in Santiago, Chile. The age range ranges from 17 to 27 years. The technique of the survey was used and the instrument used was a questionnaire of the use of scientific knowledge. The results indicate that the use of scientific knowledge of students studying differential education is similar in relation to their counterparts from another university. In addition, the levels reached in the search of information, the transfer of knowledge and the contribution to the knowledge in relation to other professional careers of education sciences are also similar. The results suggest more deeply insightful research skills and attitudes from the initial levels in differential education students, so that in the future they can perform successfully in their professional activities.Los objetivos del estudio fueron describir el conocimiento científico de estudiantes de pregrado de Educación Diferencial y compararlos con otros estudios nacionales. Se estudió a 79 estudiantes de Educación Diferencial de una Universidad de Santiago (Chile). Fueron seleccionados de forma no probabilística (intencionada) 79 (02 hombres y 77 mujeres) estudiantes de pre grado de ingreso año 2017 de la carrera de Educación Diferencial de la Universidad Católica Silva Henríquez (UCSH) de Santiago de Chile. El rango de edad oscila entre 17 a 27 años. Se utilizó la técnica de la encuesta y el instrumento utilizado fue un cuestionario del uso del conocimiento científico. Los resultados indican que el uso del conocimiento científico de los alumnos que estudian Educación Diferencial es similar en relación a sus contrapartes de otra universidad. Además, los niveles alcanzados en la búsqueda de información, la transferencia del conocimiento y la contribución al conocimiento en relación a otras carreras profesionales de ciencias de la educación, también son similares. Los resultados sugieren insentivar con mayor profundidad las habilidades y actitudes investigativas desde los niveles iniciales en los estudiante de Educación Diferencial, para que en el futuro puedan desempeñarse con éxito en sus actividades profesionales

In Silico and In Vivo Evaluation of the Maqui Berry (Aristotelia chilensis (Mol.) Stuntz) on Biochemical Parameters and Oxidative Stress Markers in a Metabolic Syndrome Model

Metabolic syndrome (MetS) is a complex disease that includes metabolic and physiological alterations in various organs such as the heart, pancreas, liver, and brain. Reports indicate that blackberry consumption, such as maqui berry, has a beneficial effect on chronic diseases such as cardiovascular disease, obesity, and diabetes. In the present study, in vivo and in silico studies have been performed to evaluate the molecular mechanisms implied to improve the metabolic parameters of MetS. Fourteen-day administration of maqui berry reduces weight gain, blood fasting glucose, total blood cholesterol, triacylglycerides, insulin resistance, and blood pressure impairment in the diet-induced MetS model in male and female rats. In addition, in the serum of male and female rats, the administration of maqui berry (MB) improved the concentration of MDA, the activity of SOD, and the formation of carbonyls in the group subjected to the diet-induced MetS model. In silico studies revealed that delphinidin and its glycosylated derivatives could be ligands of some metabolic targets such as α-glucosidase, PPAR-α, and PPAR-γ, which are related to MetS parameters. The experimental results obtained in the study suggest that even at low systemic concentrations, anthocyanin glycosides and aglycones could simultaneously act on different targets related to MetS. Therefore, these molecules could be used as coadjuvants in pharmacological interventions or as templates for designing new multitarget molecules to manage patients with MetS.This work was submitted in partial fulfillment of the requirements for the Ph.D. degree of Emily Leonela Castillo García at Doctorado en Ciencias Biológicas y de la Salud (UAM-I). Emily Leonela Castillo García received financial support from CONACyT (785220)Peer reviewe

Consistent Principal Component Modes from Molecular Dynamics Simulations of Proteins

Principal component analysis is a technique widely used for studying the movements of proteins using data collected from molecular dynamics simulations. In spite of its extensive use, the technique has a serious drawback: equivalent simulations do not afford the same PC-modes. In this article, we show that concatenating equivalent trajectories and calculating the PC-modes from the concatenated one significantly enhances the reproducibility of the results. Moreover, the consistency of the modes can be systematically improved by adding more individual trajectories to the concatenated one.Fil: Cossio Pérez, Rodrigo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Palma, Juliana Isabel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pierdominici Sottile, Gustavo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

QM/MM molecular dynamics study of the galactopyranose → galactofuranose reaction catalysed by Trypanosoma cruzi UDP-galactopyranose mutase.

The enzyme UDP-Galactopyranose Mutase (UGM) catalyses the conversion of galactopyranose into galactofuranose. It is known to be critical for the survival and proliferation of several pathogenic agents, both prokaryotic and eukaryotic. Among them is Trypanosoma cruzi, the parasite responsible for Chagas' disease. Since the enzyme is not present in mammals, it appears as a promising target for the design of drugs to treat this illness. A precise knowledge of the mechanism of the catalysed reaction would be crucial to assist in such design. In this article we present a detailed study of all the putative steps of the mechanism. The study is based on QM/MM free energy calculations along properly selected reaction coordinates, and on the analysis of the main structural changes and interactions taking place at every step. The results are discussed in connection with the experimental evidence and previous theoretical studies

In silico study of Moxifloxacin derivatives with possible antibacterial activity against a resistant form of DNA gyrase from Porphyromonas gingivalis

We performed a homology modeling of the structure of a non-mutated and mutated Ser83→Phe DNA gyrase of Porphyromonas gingivalis. The model presented structural features conserved in type II topoisomerase proteins. We designed and evaluated in silico structural modifications to the core of Moxifloxacin by molecular docking, predicted toxicity and steered molecular dynamics simulations (SMD). Our results suggest that 8D derivative of Moxifloxacin could present a strong inhibitory activity in Porphyromonas gingivalis bacteria that exhibits resistance to some conventional fluoroquinolone drugs. Also, our results suggest that hydrophobic radicals in the hydroxyl group at position 3 of the quinolone core would increase the antibacterial activity of the compound when a reported mutation Ser83→Phe is present in the DNA gyrase protein. In addition, new candidates that could have a higher antibacterial activity compared to Moxifloxacin in non-resistant bacteria are proposed.Fil: Rocha Roa, Cristian Camilo. Universidad del Quindio; ColombiaFil: Cossio Pérez, Rodrigo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Molina, Diego. Universidad del Quindio; ColombiaFil: Patiño, Jorge. Universidad Antonio Nariño; ColombiaFil: Cardona, Néstor. Universidad del Quindio; Colombia. Universidad Antonio Nariño; Colombi

Detailed mechanism for the reaction catalysed by <i>Tc</i>UGM.

<p>The mechanism includes the intermediates detected by experiments as well as those whose existence was inferred from theoretical considerations. Red color is used to denote the bonds being broken (solid line) or formed (dashed line), as well as the atoms involved. The distances between these atoms are labelled because they are used to define the reaction coordinates.</p

Main species of the reaction mechanism.

<p>Main species of the reaction mechanism.</p

values for key residues at every step of the reaction mechanism shown in Fig. 2.

<p> values for key residues at every step of the reaction mechanism shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109559#pone-0109559-g002" target="_blank">Fig. 2</a>.</p

Protein targets of thiazolidinone derivatives in Toxoplasma gondii and insights into their binding to ROP18 11 Medical and Health Sciences 1108 Medical Microbiology

Background: Thiazolidinone derivatives show inhibitory activity (IC 50 ) against the Toxoplasma gondii parasite, as well as high selectivity with high therapeutic index. To disclose the target proteins of the thiazolidinone core in this parasite, we explored in silico the active sites of different T. gondii proteins and estimated the binding-free energy of reported thiazolidinone molecules with inhibitory effect on invasion and replication of the parasite inside host cells. This enabled us to describe some of the most suitable structural characteristics to design a compound derived from the thiazolidinone core. Results: The best binding affinity was observed in the active site of kinase proteins, we selected the active site of the T. gondii ROP18 kinase, because it is an important factor for the virulence and survival of the parasite. We present the possible effect of a derivative of thiazolidinone core in the active site of T. gondii ROP18 and described some characteristics of substituent groups that could improve the affinity and specificity of compounds derived from the thiazolidinone core against T. gondii. Conclusions: The results of our study suggest that compounds derived from the thiazolidinone core have a preference for protein kinases of T. gondii, being promising compounds for the development of new drugs with potential anti-toxoplasmosis activity. Our findings highlight the importance of use computational studies for the understanding of the action mechanism of compounds with biological activity.Fil: Molina, Diego. Universidad del Quindio; ColombiaFil: Cossio Pérez, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Rocha Roa, Cristian Camilo. Universidad del Quindío; ArmeniaFil: Pedraza, Lina. Universidad del Quindio; ColombiaFil: Cortes, Edwar. Universidad del Quindio; ColombiaFil: Hernández, Alejandro. Universidad del Quindio; ColombiaFil: Gómez Marín, Jorge E.. Universidad del Quindio; Colombi