Estudo in silico da interação da albumina de soro humano com o ibuprofeno

Currently, computational methods have been increasingly used to aid in the characterization of molecular biological systems, especially when they relevant to human health. Ibuprofen is a nonsteroidal antiinflammatory or broadband use in the clinic. Once in the bloodstream, most of ibuprofen is linked to human serum albumin, the major protein of blood plasma, decreasing its bioavailability and requiring larger doses to produce its antiinflamatory action. This study aimes to characterize, through the interaction energy, how is the binding of ibuprofen to albumin and to establish what are the main amino acids and molecular interactions involved in the process. For this purpouse, it was conducted an in silico study, by using quantum mechanical calculations based on Density Functional Theory (DFT), with Generalized Gradient approximation (GGA) to describe the effects of exchange and correlation. The interaction energy of each amino acid belonging to the binding site to the ligand was calculated the using the method of molecular fragmentation with conjugated caps (MFCC). Besides energy, we calculated the distances, types of molecular interactions and atomic groups involved. The theoretical models used were satisfactory and show a more accurate description when the dielectric constant ε = 40 was used. The findings corroborate the literature in which the Sudlow site I (I-FA3) is the primary binding site and the site I-FA6 as secondary site. However, it differs in identifying the most important amino acids, which by interaction energy, in order of decreasing energy, are: Arg410, Lys414, Ser 489, Leu453 and Tyr411 to the I-Site FA3 and Leu481, Ser480, Lys351, Val482 and Arg209 to the site I-FA6. The quantification of interaction energy and description of the most important amino acids opens new avenues for studies aiming at manipulating the structure of ibuprofen, in order to decrease its interaction with albumin, and consequently increase its distribution

Validação da escala de fatigabilidade percebida para avaliação da fadiga em idosas

The term fatigability concerns the degree of fatigue associated with performing an activity of any type (physical, mental, emotional and / or social). Recently scales for assessing fatigue in the English language were created, however, gaps exist regarding the validity of these scales in relation to oxygen consumption and levels of perceived fatigue. Objective: To investigate the validity of perceived fatigability scale in older women frail and non-frail by the expired gases kinetics. Methods: This is a study of type validation, where were evaluated 48 elderly. The evaluation was conducted at two different sessions. In the first, data were collected demographic partners, as well as assessment of cognitive function, physical health, and the phenotype of frailty. The second was composed by the test 6-minute walk (6MWT) associated the expired gases kinects and assessment of perceived fatigability. Statistical analysis was performed a descriptive analysis and then we used the Pearson correlation test to evaluate the relationship between the measure of perceived fatigue and variables oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (RER)before and after 6MWT. We used a linear regression model initially considering the following explanatory variable: age, Body Mass Index (BMI), presence of frailty, comorbidities, level of physical activity, distance covered in the 6MWT , the energy cost of walking and severity of fatigability on performance. Results: The final sample consisted of 44 elderly women, 4 elderly were excluded because they didn t complete all phases of this study. The mean age obtained was 75 years (± 7.2 years). There was no significant correlation between fatigability measures and the values of VO2 ( r = .09 , p = .56 ) , VCO2 ( r = .173 , p = .26 ) , RER ( r = - .121 , p = .43 ). The final linear regression model showed that the energy cost of walking, the usual level of physical activity and the performance severity of fatigability explained 83.5 % (R2 = 0.835, p < 0.01) of the variation in the perceived fatigability. Conclusion: Our findings indicate a relationship between greater severity of fatigability and lower levels of physical activity and increased energy cost in walking, suggesting that the fatigability analyses using a simple numeric scale is valid and viable for assessment of fatigue in older women

Estudo in silico das interações da protease NS3-NS2B de DENV-2 com o inibidor peptídico Bz-nKRR-H com finalidades terapêuticas

Dengue virus is an important patogen that causes Dengue desease in all world, and belongs to Flavivirus gender. The virus consists of enveloped RNA with a single strand positive sense, 11Kb genome. The RNA is translated into a polyprotein precursor, wich is cleaved into 3 structural proteins (C, prM e E) and 7 non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B e NS5). The NS3 is a multifunctional protein, that besides to promote the polyprotein precursor cleavage, also have NTPase, helicase and RTPase activity. The NS3 needs a hydrophilic segment of 40 residues from the transmembrane NS2B protein (who acts like cofator) to realize this functions. Actually, there's no vacines available on the market, and the treatment are just symptomatic. The tetrapeptide inhibitor Bz-Nle-Lys-Arg-Arg-H (Ki de 5,8-7,0 M) was showed as a potent inhibitor μ for NS3prot in Dengue virus. That is a inteligent alternative to treat the dengue desease. The present work aimed analyse the interactions of the ligand bounded to the activity site to provid a clear and depth vision of that interaction. For this purpouse, it was conducted an in silico study, by using quantum mechanical calculations based on Density Functional Theory (DFT), with Generalized Gradient approximation (GGA) to describe the effects of exchange and correlation. The interaction energy of each amino acid belonging to the binding site to the ligand was calculated the using the method of molecular fragmentation with conjugated caps (MFCC). Besides energy, we calculated the distances, types of molecular interactions and atomic groups involved. The theoretical models used were satisfactory and show a more accurate description when the dielectric constant = 20 ε and 80 was used. The results demonstrate that the interaction energy of the system reached convergence at 13.5 A. Within a radius of 13,5A the most important residues were identified. Met49, Met84 and Asp81 perform interactions of hydrogen with the ligant. The Asp79 and Asp75 residues present high energy of attraction. Arg54, Arg85 and Lys 131 perform hydrogen interactions with the ligand, however, appear in BIRD graph having high repulsion energy with the inhibitor. The data also emphasizes the importance of residue Tyr161 and the involvement of the catalytic triad composed by Asp75, His51 and Ser135