The prostaglandins inside inflamed tissues are produced by cyclooxygenase-2 (COX-2), making it an important target for improving anti-inflammatory medications over a long period. Adverse effects have been related to the traditional usage of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of inflammation, mainly centered around gastrointestinal (GI) complications. The current research involves the creation of a virtual library of innovative molecules showing similar drug properties via a structure-based drug design. A library that includes five novel derivatives of Diclofenac was designed. Subsequently, molecular docking through the Glide module and determining the binding free energy implementing the Prime-MMGBSA module by the Schrödinger software package was used to identify compounds that showed marked specificity towards the COX-2 isoform. In addition, the ligands are subject to evaluation of their drug-like properties and ADMET (absorption, distribution, metabolism, excretion, and toxicity) characteristics using the QikProp module. Finally, molecular dynamics simulation has been calculated for the best molecule. The docking results indicated that all compounds own a predictive capability for specific binding to the COX-2 enzyme compared to the standard drug with a docking score range from -10.07 to -10.66 Kcal/mole, thus potentially overcoming the limitations imposed previously by the drugs currently used in clinical use. The ADMET analysis of the virtually active compounds demonstrated an acceptable drug-like profile and desirable pharmacokinetics properties. MM/GBSA calculation revealed that all the suggested compounds exhibited favorable free binding energies (-49.150 to - 60.185 Kcal/mole), indicating their strong potential to fit well into the COX-2 receptor. Finally, the MD simulation study revealed that compound 1 had perfect alignment with COX-2 receptor. The findings indicated that the compounds possess a predictive capability for specific binding to the COX-2 enzyme, thus potentially surmounting the restrictions imposed by the drugs currently employed in clinical use.
It has increasingly been recognised that the future developments in geospatial data handling will centre on geospatial data on the web: Volunteered Geographic Information (VGI). The evaluation of VGI data quality, including positional and shape similarity, has become a recurrent subject in the scientific literature in the last ten years. The OpenStreetMap (OSM) project is the most popular one of the leading platforms of VGI datasets. It is an online geospatial database to produce and supply free editable geospatial datasets for a worldwide. The goal of this paper is to present a comprehensive overview of the quality assurance of OSM data. In addition, the credibility of open source geospatial data is discussed, highlight
... Show MoreIn this study, the thermal buckling behavior of composite laminate plates cross-ply and angle-ply all edged simply supported subjected to a uniform temperature field is investigated, using a simple trigonometric shear deformation theory. Four unknown variables are involved in the theory, and satisfied the zero traction boundary condition on the surface without using shear correction factors, Hamilton's principle is used to derive equations of motion depending on a Simple Four Variable Plate Theory for cross-ply and angle-ply, and then solved through Navier's double trigonometric sequence, to obtain critical buckling temperature for laminated composite plates. Effect of changing some design parameters such as, ortho
... Show MoreConstruction of artificial higher order protein complexes allows sampling of structural architectures and functional features not accessible by classical monomeric proteins. Here, we combine in silico modelling with expanded genetic code facilitated strain promoted azide-alkyne cycloaddition to construct artificial complexes that are structurally integrated protein dimers and demonstrate functional synergy. Using fluorescent proteins sfGFP and Venus as models, homodimers and heterodimers are constructed that switched ON once assembled and display enhanced spectral properties. Symmetrical crosslinks are found to be important for functional enhancement. The determined molecular structure of one artific
The introduction of concrete damage plasticity material models has significantly improved the accuracy with which the concrete structural elements can be predicted in terms of their structural response. Research into this method's accuracy in analyzing complex concrete forms has been limited. A damage model combined with a plasticity model, based on continuum damage mechanics, is recommended for effectively predicting and simulating concrete behaviour. The damage parameters, such as compressive and tensile damages, can be defined to simulate concrete behavior in a damaged-plasticity model accurately. This research aims to propose an analytical model for assessing concrete compressive damage based on stiffness deterioration. The prop
... Show MoreThe research aims to determine the mix of production optimization in the case of several conflicting objectives to be achieved at the same time, therefore, discussions dealt with the concept of programming goals and entrances to be resolved and dealt with the general formula for the programming model the goals and finally determine the mix of production optimization using a programming model targets to the default case.
In this work, diamond-like carbon (DLC) thin films were prepared from Cyclohexane. Thin films were deposited on quartz substrate by atmospheric pressure Argon plasma jet system. The plasma jet system was applying high voltage sinusoidal waves of frequency 28 kHz and potential difference of 7.5kV peak to peak across the electrodes. The effect of annealing at 400, 500 and 600 °C under vacuum for two hours on optical properties and structural properties of the DLC thin films were investigated. This effect was clarified by X-ray diffraction (XRD), FTIR, UV-Visible absorption, Scanning Electron Microscopy (SEM) and Raman Spectroscopy. The X-ray diffraction patterns for the annealing DLC thin films show two broad peaks at 2θ, 26.62° and 51.58
... Show MoreThe higher education has become an enterprise integrate system that described as knowledge society, the essential part in its electronic and virtual format in the shadow of globalization challenges with its various dimensions . Until the logical ryles aboat a strategic partnership between the Iraqi higher education establishments and their international equivalent ones Strategic windows should be invested for the purpose of enhancing the quality of higher education in a sustainable way. This forms a challenge before the international education leaders on the social, operational and establishment's level to determinte knowledge gap, observing, diagnosing and processing in the present and future, e
... Show MoreThe main idea that led me to write such research paper within the framework of Germanic linguistics is that I have not found any topic dealing with the term correlate in the German language, except in several articles in linguistic journals as well as one topic in a book describing the use of such a linguistic phenomenon in the language system. The research initially deals with the definition of the correlate at the level of the German language system. Correlate is unity describes specific relation of two sentences and identifies denoted constructs. Correlate is called a placeholder at the syntactic level because it does not occupy its original topological fields in the syntactic structure. The correlate (es) or the prepositiona
... Show MoreThe fractional free volume (Fh) in polystyrene (PS) as a function of neutron -irradiation dose has been measured, using positron annihilation lifetime (PAL) method. The results show that Fh values decreased with increasing n-irradiation dose up to a total dose of 501.03× 10-2 Gy.
A percentage reduction of 2.14 in Fh values is noticed after the initial n-dose corresponding to a percentage reduction in the free volume equal to 42.14/Gy.
The total n-dose induces a percentage reduction of 7.26, corresponding to a percentage reduction of 1.45/Gy. These results indicate that cross -linking is the predominant process induced by n-irradiation.
The results suggest that n-irradiation induces structure changes in PS, causing cross-linking