New Molecular Screening Approach for Discovery of Novel CycloOxygenase-2 Inhibitors through Multi Linear Regression Models

Background: Inflammation is basically caused with conversion of Arachidonic acid into Prostaglandin H2 by CycloOxygenase. In this study a new algorithmic procedure is applied in order to screen molecules not only with high affinity to COX-2, but also different from their ancestor compounds.Methods: NSAIDs, COX-1 and COX-2 molecules were downloaded from Drug Bank and Protein Data Bank. Drugs were docked with both proteins by FlexX software. Top 10 molecules with lowest COX-2 interaction energies and highest differences between COX-2 and COX-1 IEs were selected for structural similarity searches in PUBCHEM and ENCANCED NCI databases. Second generation molecules were docked with proteins once again. Compounds with lower IEs than parents, were collected. Bioactivities and bioavailabilities of compounds were analyzed by PASS software and Lipinski rules. A best multi linear regression model was developed based on some physicochemical descriptors for further studies.Results: 50 NSAIDs were selected and 2000 similar molecules gathered. Screening the molecules based on Lipinski rules, bioactivities and drug likenesses, a trustable BMLR model was developed with more than 80% accuracy including following descriptors: Log P, Log D, Molar Refractivity, Polarity Number, and Aromaticity Ratio. Finally, 6 compounds were selected as best structurally new compounds for further in vitro analysis.Conclusions: Final molecules having high druglikeness and affinity and structurally different from their ancestors, can be used in order to develop new lead compounds with higher selectivity

Computational vaccinology and epitope vaccine design by immunoinformatics

Human immune system includes variety of different cells and molecules correlating with other body systems. These instances complicate the analysis of the system; particularly in postgenomic era by introducing more amount of data, the complexity is increased and necessity of using computational approaches to process and interpret them is more tangible.Immunoinformatics as a subset of bioinformatics is a new approach with variety of tools and databases that facilitate analysis of enormous amount of immunologic data obtained from experimental researches. In addition to directing the insight regarding experiment selections, it helps new thesis design which was not feasible with conventional methods due to the complexity of data. Considering this features immunoinformatics appears to be one of the fields that accelerate the immunological research progression.In this study we discuss advances in genomics and vaccine design and their relevance to the development of effective vaccines furthermore several division of this field and available tools in each item are introduced

A review on proteomics analysis to reveal biological pathways and predictive proteins in sulfur mustard exposed patients: roles of inflammation and oxidative stress

Sulfur mustard (SM) is a mutagenic compound that targets various organs. Although it causes a wide range of abnormalities, cellular and molecular mechanisms of its action are not-well-understood. Oxidation of DNA, proteins, lipids, as well as depletion of cellular nicotinamide adenine dinucleotide (NAD), antioxidants and increase of intracellular calcium are the hypothesized mechanisms of its action at the acute phase of injury. In this review, the proteome analysis of SM toxicity has been considered. We selected articles that considered proteomics analysis of SM toxicity with two-dimensional gel electrophoresis (2DE) followed by mass spectrometry. Our search yielded nine related articles, four original in vitro and five human studies. The results of these studies have revealed a change in expression pattern of various proteins such as haptoglobin, amyloid A1, surfactant proteins, S100 proteins, apolipoprotein, Vit D binding protein, transferrin, alpha 1 antitrypsin, protein disulfide isomerase and antioxidant enzymes in patients who were exposed to SM about 30 years ago. Most of these proteins are up- or down-regulated in response to excessive production of reactive oxygen species (ROS) and oxidative stress (OS). There is a tight link between the expression pattern of these proteins with accumulation of leukocytes, inflammatory conditions, antioxidant depletion, mitochondrial deficiency, as well as increased expression or activity of several proteases such as caspases and matrix metalloproteinases (MMPs). Therefore, excessive production of ROS and OS along with chronic inflammatory may be the long-term toxic effects of SM following acute exposure