Raquel da Luz Dias

Evaluation of molecular docking using polynomial empirical scoring functions.

Molecular docking simulations are of pivotal importance for analysis of protein-ligand interactions and also an essential resource for virtual-screening initiatives. In molecular docking simulations several possible docked structures are generated, which create an ensemble of structures representing binary complexes. Therefore, it is crucial to find the best solution for the simulation. One approach to this problem is to employ empirical scoring function to identify the best docked structure. It is expected that scoring functions show a descriptive funnel-shaped energy surface without many false minima to impair the efficiency of conformational sampling. We employed this methodology against a test set with 300 docked structures. Docking simulations of these ligands against enzyme binding pocket indicated a funnel-shaped behavior of the complexation for this system. This review compares a set of recently proposed polynomial empirical scoring functions, implemented in a program called POLSCORE, with two popular scoring function programs (XSCORE and DrugScore). Overall comparison indicated that POLSCORE works better to predict the correct docked position, for the ensemble of docked structures analyzed in the present work.

Structural studies of human purine nucleoside phosphorylase: towards a new specific empirical scoring function.

Human purine nucleoside phosphorylase (HsPNP) is a target for inhibitor development aiming at T-cell immune response modulation. In this work, we report the development of a new set of empirical scoring functions and its application to evaluate binding affinities and docking results. To test these new functions, we solved the structure of HsPNP and 2-mercapto-4(3H)-quinazolinone (HsPNP:MQU) binary complex at 2.7A resolution using synchrotron radiation, and used these functions to predict ligand position obtained in docking simulations. We also employed molecular dynamics simulations to analyze HsPNP in two conditions, as apoenzyme and in the binary complex form, in order to assess the structural features responsible for stability. Analysis of the structural differences between systems provides explanation for inhibitor binding. The use of these scoring functions to evaluate binding affinities and molecular docking results may be used to guide future efforts on virtual screening focused on HsPNP.

Impacto do exercício físico isolado e combinado com dieta sobre os níveis séricos de HDL, LDL, colesterol total e triglicerídeos

Adequate eating habits and physical exercise have a beneficial effect on dislipidemies. When associated, they might even optimize changes to the plasmatic lipoproteic profile, apart of which they are moderate-cost interventions if compared to drug-based and high-tech depending treatments. The present study aims at assessing the impact of physical exercise as isolated and combined with a diet on the lipidic profile of overweight/obese individuals. Tn observational analytical retrospective study has looked into the evolution of the lipidic profile and weight over a period of 3 to 6 months of 30 individuals divided in two groups: the exercise group (physical exercise practice) and the diet group (physical exercise associated with a nutritional intervention). Significant statistical reductions were found in the CT (-14.4 mg/dl; P=0,022) and in the LDL-c (-20.9 mg/dl; P = 0,013) for the components in the exercise group. Such reduction has also occurred regarding the CT/HDL-c (-0,9; P = 0,005) ratio for the components of the diet group. The increase in the HDL-c levels was observed only in the diet group (+4.2 mg/dl). In this same group a decrease in the CT (-8 mg/dl) and in the LDL-c (-9,8 mg/dl) was observed as well as a weight reduction (-2.6 Kg), however, such results have not been statistically significant. Regarding the TG levels, there was no evidence for a positive evolution in either group. As a conclusion, the isolated effect of physical exercise was more evident concerning the variables CT and LDL-c. The TG did not undergo positive modifications upon the exclusive practice of physical exercise or with their association with the diet. As for variables HDL-c and weight, the combination of diet and physical exercise has proven to bring enhanced benefits.

Molecular modeling and dynamics simulations of PNP from Streptococcus agalactiae

This work describes for the first time a structural model of purine nucleoside phosphorylase from Streptococcus agalactiae (SaPNP). PNP catalyzes the cleavage of N-ribosidic bonds of the purine ribonucleosides and 2-deoxyribonucleosides in the presence of inorganic orthophosphate as a second substrate. This enzyme is a potential target for the development of antibacterial drugs. We modeled the complexes of SaPNP with 15 different ligands in order to determine the structural basis for the specificity of these ligands against SaPNP. The application of a novel empirical scoring function to estimate the affinity of a ligand for a protein was able to identify the ligands with high affinity for PNPs. The analysis of molecular dynamics trajectory for SaPNP indicates that the functionally important motifs have a very stable structure. This new structural model together with a novel empirical scoring function opens the possibility to explorer larger library of compounds in order to identify the new inhibitors for PNPs in virtual screening projects.

Evaluation of ligand-binding affinity using polynomial empirical scoring functions.

Assessing protein-ligand interaction is of great importance for virtual screening initiatives in order to discover new drugs. The present work describes a set of empirical scoring functions to assess the binding affinity, involving terms for intermolecular hydrogen bonds and contact surface. The results show that our methodology works better to predict protein-ligand affinity when compared with XSCORE, a popular empirical scoring function.

Molecular Modeling as a Tool for Drug Discovery

With the progression of structural genomics projects, comparative modeling remains an increasingly important method of choice to obtain 3D structure of proteins. It helps to bridge the gap between the available sequence and structure information by providing reliable and accurate protein models. Comparative modeling based on more than 30% sequence identity is now approaching its natural template-based limits and further improvements require the development of effective refinement techniques capable of driving models toward native structure. For difficult targets, for which the most significant progress in recent years has been observed, optimal template selection and alignment accuracy are still the major problems. The past year has seen a maturation of molecular modeling, with an increasing number of comparative studies between established methods becoming possible, together with an explosion of new works especially in the areas of combinatorial chemistry and molecular diversity. To achieve this, knowledge about three-dimensional protein structures is crucial for the understanding of their functional mechanisms, and for a rational drug design. This review described recent progress in molecular modeling methodology.

Bioinformatics Tools for Screening of Antiparasitic Drugs

Drug development has become the Holy Grail of many structural bioinformatics groups. The explosion of information about protein structures, ligand-binding affinity, parasite genome projects, and biological activity of millions of molecules opened the possibility to correlate this scattered information in order to generate reliable computational models to predict the likelihood of being able to modulate a target with a small-molecule drug. Computational methods have shown their potential in drug discovery and development allied with in vitro and in vivo methodologies. The present review discusses the main bioinformatics tools available for drug discovery and development.

Molecular modeling, dynamics and docking studies of Purine Nucleoside Phosphorylase from Streptococcus pyogenes

Purine Nucleoside Phosphorylase (PNP) catalyzes the reversible phosphorolysis of N-glycosidic bonds of purine nucleosides and deoxynucleosides, except for adenosine, to generate ribose 1-phosphate and the purine base. PNP has been submitted to intensive structural studies. This work describes for the first time a structural model of PNP from Streptococcus pyogenes (SpPNP). We modeled the complexes of SpPNP with six different ligands in order to determine the structural basis for specificity of these ligands against SpPNP. Molecular dynamics (MD) simulations were performed in order to evaluate the overall stability of SpPNP model. The analysis of the MD simulation was assessed mainly by principal component analysis (PCA) to explore the trimeric structure behavior. Structural comparison, between SpPNP and human PNP, was able to identify the main features responsible for differences in ligand-binding affinities, such as mutation in the purine-binding site and in the second phosphate-binding site. The PCA analysis suggests a different behavior for each subunit in the trimer structure.

Perfil nutricional de pacientes adultos e idosos admitidos em um hospital universitário

Objective: To identify the nutritional status of adults and elderly patients admitted in an university hospital. Materials and Methods: This is a cross-sectional, retrospective and descriptive study. The nutritional assessment was conducted by using the body mass index (BMI) and the subjective global assessment (SGA), which classifies patients into three categories: well nourished (A), moderately or suspected of being malnourished (B) or severely malnourished (C). All data (SGA, BMI and primary condition) were collected from information present in the evaluation forms filled in the nutritional routine, which are performed within seventy-two hours after admission. The study was approved by the Scientific and Ethics Committee for Research of PUCRS. Results: The study included 32 adults and 36 elderly (n=68). In relation to the SGA, 46,9% of adults were classified as well nourished (A) and 53,1% as moderately (or suspected of being) malnourished (B). Among elderly patients, 25% were classified as well nourished (A) and 75% as moderately (or suspected of being) malnourished (B). The BMI showed 37,5% of adults as eutrophic and 62,5% as overweight or obesity; the elderly were classified as 50% eutrophic, 36,1% overweight and 13,9% underweight. Conclusion: The nutritional status of the studied patients was characterized by the high prevalence of nutritional risk and overweight/obesity in both groups. This reality seems to translate, at the hospital level, the situation of nutritional transition experienced in our country today. In addition, the results point the importance of using more than one method of nutrition screening in patients admitted in hospitals, in order to obtain greater precision in the assessment.

Video Production and Video Tutorials in Professional Health Education: A Mobile Learning Experience

Motivated by the significant increase in the presence of mobile devices in the classroom and the opportunity to use these resources to improve and streamline the process of teaching and learning, this paper proposes a pedagogical use of mobile technologies, specifically, tablets in the class. The proposal was developed under LabsMoveis, a subproject of the LabTEAR Project, and applied in an undergraduate program of the Health area. The use of tablets in the University classroom contributed to the expansion of general and specific cognitive abilities, stimulating creativity and leadership for the learners, while enhancing their initiatives to solve problems.