Computational Study of pKa shift of Aspartate residue in Thioredoxin: Role of Configurational Sampling and Solvent Model

Alchemical free energy calculations are widely used in predicting pKa, and binding free energy calculations in biomolecular systems. These calculations are carried out using either Free Energy Perturbation (FEP) or Thermodynamic Integration (TI). Numerous efforts have been made to improve the accuracy and efficiency of such calculations, especially by boosting conformational sampling. In this paper, we use a technique that enhances the conformational sampling by temperature acceleration of collective variables for alchemical transformations and applies it to the prediction of pKa of the buried Asp 26 residue in thioredoxin protein. We discuss the importance of enhanced sampling in the pKa calculations. The effect of the solvent models in the computed pKa values is also presented.Comment: 29 pages with 13 figure

IDENTIFICATION OF NOVEL INHIBITORS AGAINST POTENTIAL TARGETS OF CAMPYLOBACTER JEJUNI

Objective: The aim of the present study is the structure identification of UDP-N-acetyl muramate dehydrogenase and 4-hydroxy-3-methylbut-2-enyl diphosphate reductase for Campylobacter jejuni and designing their inhibitors using docking and simulation studies.Methods: Uniprot, BLAST P, Discovery Studio, Verify 3D and Maestro Schrödinger suit have been used for structure identification, validation and docking studies.Results: The structures of UDP-N-acetylmuramic dehydrogenase and 4-hydroxy-3-methylbut-2-enyl diphosphate reductase were predicted and validated generating 87.80% and 85.82% score respectively. For 4-hydroxy-3-methylbut-2-enyl diphosphate reductase, HTVS resulted in 5801 compounds while SP and XP resulted in 5781 ligands. For UDP-N-acetylmuramate dehydrogenase, HTVS resulted in 5474 compounds whereas SP and XP resulted in 5359 ligands.Conclusion: The structures of UDP-N-acetylmuramate dehydrogenase and 4-hydroxy-3-methylbut-2-enyl diphosphate reductase were detected and verified. The list of top 10 inhibitors was acquired that can be considered as putative and potential drug targets.Keywords: Campylobacter jejuni, Structure prediction, Active site, Docking, Inhibitor.Â

Neutrino Mass Matrices with a Texture Zero and a Vanishing Minor

We study the implications of the simultaneous existence of a texture zero and a vanishing minor in the neutrino mass matrix. There are thirty six possible texture structures of this type, twenty one of which reduce to two texture zero cases which have, already, been extensively studied. Of the remaining fifteen textures only six are allowed by the current data. We examine the phenomenological implications of the allowed texture structures for Majorana type CP-violating phases, 1-3 mixing angle and Dirac type CP-violating phase. All these possible textures can be generated through the seesaw mechanism and realized in the framework of discrete abelian flavor symmetry. We present the symmetry realization of these texture structures.Comment: To appear in Phys. Rev.

DEVELOPMENT AND VALIDATION OF UV-SPECTROPHOTOMETRIC METHOD FOR ESTIMATION OF HYDROQUINONE IN BULK, MARKETED CREAM AND PREAPARED NLC FORMULATION

Objective: The aim of the present work was to develop a simple, rapid, accurate and economical UV-visible spectrophotometric method for the determination of hydroquinone (HQ) in its pure form, marketed formulation as well as in the prepared nanostructured lipid carrier (NLC) systems and to validate the developed method. Methods: HQ was estimated at UV maxima of 289.6 nm in pH 5.5 phosphate buffer using UV-Visible double beam spectrophotometer. Following the guidelines of the International Conference on Harmonization (ICH), the method was validated for various analytical parameters like linearity, precision, and accuracy robustness, ruggedness, limit of detection, quantification limit, and formulation analysis. Results: The obtained results of the analysis were validated statistically. Recovery studies were performed to confirm the accuracy of the proposed method. In the developed method, linearity over the concentration range of 5-40 μg/ml of HQ was observed with the correlation coefficient of 0.998 and found in good agreement with Beer Lambert's law. The precision (intra-day and inter-day) of the method was found within official RCD limits (RSD<2%). Conclusion: The sensitivity of the method was assessed by determining the limit of detection and limit of quantification. It could be concluded from the results obtained that the purposed method for estimation of HQ in pure form, in the marketed ointment and in the prepared NLC-formulation was simple, rapid, accurate, precise and economical. It can be used successfully in the quality control of pharmaceutical formulations and for the routine laboratory analysis

A study on prevalence of metabolic syndrome in general population in Western Uttar Pradesh, India

Background: A global transition in the disease pattern has been observed, where the relative impact of infectious disease is decreasing while chronic disease like cardiovascular disease and diabetes are increasingly dominating the disease pattern. Metabolic syndrome (MetS) is a complex web of metabolic factors that are associated with a 2-fold increased risk of CVD and 5-fold risk of diabetes.Methods: A total of 350 patients were included and a cross sectional study was conducted to identify metabolic syndrome prevalence and to evaluate risk factor for development of metabolic syndrome.Results: 48% of participants were male and 52% were female our results showed a BMI of 22.11±3.57 in male and 22.16±2.82 in females. The overall prevalence of overweight was 31%. This study also showed significantly higher rate of metabolic syndrome in older age group i.e. 9.38% in age group of 30-39 years and 26.98% in 60-70 age group. Proportionally more subjects with MetS (74%) have sedentary life style as compared to those without MetS (54%).Conclusions: The prevalence of Metabolic syndrome varies among ethnic groups. Indians are at high risk for ASCVD and their predisposition. The high prevalence of overweight and obesity was one of the major driving force in the development of MetS

Importance of silicon in combating a variety of stresses in plants: A review

The abundance of silicon (Si) in the earth's crust is found as silicon dioxide (SiO2). But this abundance of Si is not a sign that the plants take up an adequate amount of Si. This review article incorporates research based on Si to understand the importance of Si in plants under various stress conditions and its role in sustainable agricultural production. Si's application is considered a better approach to providing stress tolerance to plants under stress conditions. The review describes the different phases of Si, its absorption, transport in plants, and its various mechanisms of action to tolerate specific stresses. The uptake and transport of Si through various Si transporters have also been reported. This review also discusses the various mechanisms of Si under biotic or abiotic stress in different plants. The application of Si improves soil quality and soil health and enhances the soil microbial population. In addition, the role of Si in the upregulation and down-regulation of proteins under stressful conditions has also been reported. The information can help to better understand the importance and mechanism of Si in plants and its application in agriculture

Graphene-based nanocomposites: An efficient detoxification agent for heavy metal removal from wastewater

Numerous scientific and technological developments in wastewater treatment procedures are brought on by the shortage of clean water supplies. Heavy metals' recalcitrance in wastewater has been shown to be a difficult issue. Further, drinking water quality must be at its highest for human health to be at its best; nevertheless, a number of human activities are continuously degrading it, which has an effect on human health either directly or indirectly. Because heavy metals are the primary causes of many chronic illnesses and have a tendency to bio accumulate, they are giving rise to a lot of worries. Technologies from all over the world are being developed to address the demand for clean drinking water. The objective of the current study is to raise awareness of the need to remove dangerous dense metals from various types of wastewater and the application of modified graphene nanocomposite for their adsorption-based removal. Graphene-based nanocomposite materials have been picked for this application due to their large surface area, superior mechanical strength, and reactivity towards polar and nonpolar contaminants for the electrostatic emission of the heavy metal ions arsenic (As), chromium (Cr), copper (Cu), and lead (Pb)