Computer-aided design of selective COX2 inhibitors: molecular docking of structurally diverse cyclooxygenase-2 inhibitors using FlexX

Motivation: Three-dimensional structures of pharmacologically important macromolecules offer a route to the discovery of new drugs. Understanding the macromolecule-ligand interactions and validation of method used for docking and virtual screening of chemical databases is crucial step in structure-based design. We therefore carried out molecular docking for a set of eighty two structurally diverse COX-1/COX-2 inhibitors including traditional NSAIDs and the recent developed coxibs using FlexX method to find out how good this method differentiate between the active and inactive compounds. Method: FlexX is one of the fast flexible docking method that uses an incremental construction algorithm to place ligands into an active site. The scoring function (empirical binding free energy) of the flexX used to estimate the free binding energy of the protein-ligand complex is called F_score. Results: Reproducibility of the experimental conformations of the bound ligands such as SC-558, indomethacin, flurbiprofen indicates the better performance of FlexX method. Good correlation between the standard FlexX score (F_score) and the COX-2 inhibitory activity (pIC50) was observed. Simple linear regression analysis provided the correlation coefficient values of 0.731 and 0.670 for two classes of COX-2 inhibitors. Conclusions: Flexible docking of eighty two structurally diverse COX-2 inhibitors have been successfully carried out. Some false positives and false negatives were observed but considering the limitations of the available docking programs, the results are encouraging. The detailed analysis of the resulted COX-2-ligand complexes may improve our knowledge in understanding the binding interactions in detail. Thus, this study will be useful for the design of novel COX-2 inhibitors based on docking and the resulted bioactive conformations of the ligands will be useful in building structure-based 3-D QSAR model

An Optimal HSI Image Compression using DWT and CP

The compression of hyperspectral images (HSIs) has recently become a very attractive issue for remote sensing applications because of their volumetric data. An efficient method for hyperspectral image compression is presented. The proposed algorithm, based on Discrete Wavelet Transform and CANDECOM/PARAFAC (DWT-CP), exploits both the spectral and the spatial information in the images. The core idea behind our proposed technique is to apply CP on the DWT coefficients of spectral bands of HSIs. We use DWT to effectively separate HSIs into different sub-images and CP to efficiently compact the energy of sub-images. We evaluate the effect of the proposed method on real HSIs and also compare the results with the well-known compression methods. The obtained results show a better performance when comparing with the existing method PCA with JPEG 2000 and 3D SPECK.DOI:http://dx.doi.org/10.11591/ijece.v4i3.6326

An application of Pascal distribution involving Kamali type related to leaf like domain

This paper aims to study the Geometric properties of analytic function in the open unit disk. In the present investigation, we obtain some geometric properties of Pascal distribution involving Kamali type related to leaf like domain. In this paper, we find coefficient inequality, Radii Properties, convolution product, partial sum of the class $\Sigma(\delta, \Phi, \beta, s, t, m)$. Furthermore, we examine the distortion bounds belonging to the same class

Retinal Blood Vessels Extraction Based on Curvelet Transform and by Combining Bothat and Tophat Morphology

Retinal image contains vital information about the health of the sensory part of the visual system. Extracting these features is the first and most important step to analysis of retinal images for various applications of medical or human recognition. The proposed method consists of preprocessing, contrast enhancement and blood vessels extraction stages. In preprocessing, since the green channel from the coloured retinal images has the highest contrast between the subbands so the green component is selected. To uniform the brightness of image adaptive histogram equalization is used since it provides an image with a uniformed, darker background and brighter grey level of the blood vessels. Furthermore Curvelet transforms is used to enhance the contrast of an image by highlighting its edges in various scales and directions. Eventually the combination of Bothat and Tophat morpholological function followed by local thresholding is provided to classify the blood vessels. Hence the retinal blood vessels are separated from the background image.DOI:http://dx.doi.org/10.11591/ijece.v4i3.632

Subclasses of starlike functions associated with a fractional calculus operator involving Caputo's fractional differentiation

In this paper, we introduce a new class of functions which are analytic and univalent with negative coefficients defined by using certain fractional operators descibed in the Caputo sense and obtain coefficient estimates, extreme points, the radii of close to convexity, starlikeness and convexity and neighbourhood results for functions in this new class. In  particular, we obtain modified Hadamard product results for the function f(z) belongs to the new class in the unit disc

A study on the defluoridation in water by using natural soil

Removal of excess fluoride (F−) from the water has been attempted by several authors by using different materials both natural and artificial. The main aim of this paper was to attempt the fluoride removal by using the locally available red soil adopting column method. The red soil was mixed in different proportion with sand in order to increase the porosity and permeability property of the medium. It was optimized for 4:1 ratio of red soil to sand and it was used for the following experiment. The experiment was conducted in 11 batches for a period of about 9,213 min. Fresh standard solution of F was used in each batch, prepared from Orion 1,000 ppm solution. The samples were collected and analyzed for pH, EC (Electrical Conductivity) and HCO3. Rate of flow of water and efficiency of adsorption were calculated and compared with the fluoride removal capacities of the medium. The medium used for the fluoride removal was subjected to FTIR analysis before and after the experiment. The variation of IR spectrum before and after treatment signifies the changes in the OH bonding between Al and Fe ions present in the soil. The variation in pH decreased during the course of defluoridation. Higher F removal was noted when flow rate was lesser. An attempt on the regeneration of the fluoride adsorbed soil was also made and found to be effective

Acetylation and phosphorylation of human TFAM regulate TFAM-DNA interactions via contrasting mechanisms

Mitochondrial transcription factor A (TFAM) is essential for the maintenance, expression and transmission of mitochondrial DNA (mtDNA). However, mechanisms for the post-translational regulation of TFAM are poorly understood. Here, we show that TFAM is lysine acetylated within its high-mobility-group box 1, a domain that can also be serine phosphorylated. Using bulk and single-molecule methods, we demonstrate that site-specific phosphoserine and acetyllysine mimics of human TFAM regulate its interaction with non-specific DNA through distinct kinetic pathways. We show that higher protein concentrations of both TFAM mimics are required to compact DNA to a similar extent as the wild-type. Compaction is thought to be crucial for regulating mtDNA segregation and expression. Moreover, we reveal that the reduced DNA binding affinity of the acetyl-lysine mimic arises from a lower on-rate, whereas the phosphoserine mimic displays both a decreased on-rate and an increased off-rate. Strikingly, the increased off-rate of the phosphoserine mimic is coupled to a significantly faster diffusion of TFAM on DNA. These findings indicate that acetylation and phosphorylation of TFAM can fine-tune TFAM-DNA binding affinity, to permit the discrete regulation of mtDNA dynamics. Furthermore, our results suggest that phosphorylation could additionally regulate transcription by altering the ability of TFAM to locate promoter sites

A comparison of the effects of physical and chemical mutagens in sesame (Sesamum indicum L.)

Three sesame genotypes (Rama, SI 1666 and IC 21706) were treated with physical (γ-rays: 200 Gy, 400 Gy or 600 Gy) or chemical (ethyl methane sulphonate, EMS: 0.5%, 1.0%, 1.5% or 2.0%) mutagens and their mutagenic effectiveness and efficiency were estimated in the M 2 generation. The M 3 generation was used to identify the most effective mutagen and dose for induction of mutations. The average effectiveness of EMS was much higher than γ-rays. The lowest dose of γ-rays (200 Gy) and the lowest concentration of EMS (0.5%) showed the highest mutagenic efficiency in all genotypes. Analysis of the M 3 generation data based on parameters such as the variance ratio and the difference in residual variances derived from the model of Montalván and Ando indicated that 0.5% concentration of EMS was the most effective treatment for inducing mutations

Rapid and Accurate Prediction and Scoring of Water Molecules in Protein Binding Sites

Water plays a critical role in ligand-protein interactions. However, it is still challenging to predict accurately not only where water molecules prefer to bind, but also which of those water molecules might be displaceable. The latter is often seen as a route to optimizing affinity of potential drug candidates. Using a protocol we call WaterDock, we show that the freely available AutoDock Vina tool can be used to predict accurately the binding sites of water molecules. WaterDock was validated using data from X-ray crystallography, neutron diffraction and molecular dynamics simulations and correctly predicted 97% of the water molecules in the test set. In addition, we combined data-mining, heuristic and machine learning techniques to develop probabilistic water molecule classifiers. When applied to WaterDock predictions in the Astex Diverse Set of protein ligand complexes, we could identify whether a water molecule was conserved or displaced to an accuracy of 75%. A second model predicted whether water molecules were displaced by polar groups or by non-polar groups to an accuracy of 80%. These results should prove useful for anyone wishing to undertake rational design of new compounds where the displacement of water molecules is being considered as a route to improved affinity