Volume-4, Issue-2 March - April 2015
International Journal of Computational Bioinformatics and In Silico Modeling
ABSTRACT: Acacetin (5,7-dihydroxy-4'-methoxyflavone), a flavonoid compound, has anti-peroxidative and anti-inflammatory effects. Few results revealed the anti-migration and anti-invasion effects of acacetin, which may act as a promising therapeutic agent for the treatment of lung cancer. Mitogen-activated protein kinase (MAPK) cascades are key signaling pathways involved in the regulation of normal cell proliferation, survival and differentiation. Aberrant regulation of MAPK cascades contribute to cancer and other human diseases. In particular, the extracellular signal-regulated kinase (ERK) MAPK pathway has been the subject of intense research scrutiny leading to the development of pharmacologic inhibitors for the treatment of cancer. MLK3 (mixed lineage kinase 3) is a MAP3K (mitogen activated protein kinase) that activates multiple MAPK pathways. In that perspective the MLK3 binding domain with small ligand molecules like acacetin is analyzed through in silico docking studies. The binding energy evaluation shows the importance of specific amino groups at various positions on the acacetin molecule. Analysing binding sites and free energy of binding produced, explains the importance of acacetin in targeting MAPK signaling pathway exhibit as a potential pharmacologic inhibitors for the treatment of cancer, specifically lung cancer.
KeyWords: in silico docking, Acacetin, MAPK (Mitogen-activated protein kinase) and MLK3 (Mixed lineage kinase 3).
How to cite: H. Mallesha et. al. In silico dstudy of Acacetin interaction with mixed-lineage protein kinase 3 (MLK3) of human non-small cell lung. Int J Comput Bioinfo In Silico Model. 4(2) 2015: 611-615
ABSTRACT: Asthma affects nearly 300 million people worldwide. The majority respond to inhaled corticosteroid treatment with or without beta-adrenergic agonists. However, a subset of 5 to 10% with severe asthma does not respond optimally to these medications. Many researcher working on Arachidonic acid metabolism leads to the generation of key lipid mediators which play a fundamental role during inflammation. The inhibition of enzymes involved in arachidonic acid metabolism has been considered as a synergistic anti-inflammatory effect with enhanced spectrum of activity. Most important enzyme involved in arachidonic acid metabolism is lipoxygenase (LOX); specifically 5-LOX pathway is the source of potent pro-inflammatory mediators. Leukotrienes (LTs) are important mediators of allergic asthma produced through 5-LOX pathway. It is known that LOX plays an important role in inflammatory response as it catalyzes the oxidation of unsaturated fatty acids, such as linoleic acid to form hydroperoxides. The natural molecule Curcumin, the major polyphenol of turmeric spice, is a member of the ginger family (Zingiberaceae) was shown to exhibit potent lipoxygenase (LOX) inhibitory activity. The search for selective LOX inhibitors may provide new therapeutic approach for inflammatory diseases. Molecular docking experiments were carried out to elucidate the molecular aspects of the observed inhibitory activities of the curcumin and its analogs against Lipoxygenase. Present findings increase the possibility that these curcumin and its analogs might serve as a beneficial starting point for the design and development of improved anti-inflammatory agents.
KeyWords: in silico docking, Curcumin, lipoxygenase (LOX), Leukotrienes (LTs) and 5-lipoxygenase activating protein (FLAP).
How to cite: H. Mallesha et. al. Molecular Docking Studies of Curcumin and its analogs as Inhibitors of Arachidonate 5-lipoxygenase for Asthma. Int J Comput Bioinfo In Silico Model. 4(2) 2015: 616-622
ABSTRACT: Grapes and their derivatives have a large and expanding worldwide market. Vitis vinifera has the potential to become a model organism for fruit trees since its genome has been sequenced and genes coding for various traits has been predicted. In the current study we made efforts to re-annotate the Vitis vinifera genome using fourth generation gene prediction tool. A total of 54216 genes were predicted which are almost twice predicted by Velasco et. al., with an average GC content of 45.51%. In further attempts we identified Transcription Factors in Vitis vinifera genome and classified these in 83 different categories. FAR1 which possess role in feedback regulation of Phytochrome-A signal, that controls anthocyanin synthesis and chloroplast development was found to be most abundant whereas no evidence was found for VARL and Zinc-clusters. In addition, we found 31% of genes that were associated with molecular function, 29% with biological process and nearly 40% with cellular components through gene ontology analysis. Total 226 genes identified which do not show their involvement in either categories of Gene Ontology. These unclassified genes found to be area of interest regarding functional characterization.
KeyWords: Vitis vinifera, gene prediction, Augustus, gene ontology, transcription factors.
How to cite: Leela Verma et. al. In silico Gene prediction in Vitis vinifera using fourth generation tool. Int J Comput Bioinfo In Silico Model. 4(2) 2015: 623-628
ABSTRACT: ACORN Program available in the CCP4 suite of programs is a comprehensive and efficient phasing procedure for the protein structure determination using seed input information with a data resolution of 1.7 Å or better. The output of ACORN phases are enough to build the entire model using the automated model building programs. OASIS is a computer program used for phasing and it works on direct method procedure to break the phase ambiguity intrinsic to SAD (or) SIR data. If the model building using ACORN phases is not enough to build the entire model then the program OASIS developed better phases from this incomplete model. Attempts have been made to use ACORN and OASIS combination to determine the structure of alkaline cellulaseapo form (PDB-ID: 1g01) and cytokine (PDB-ID: 4N1D) at a resolution of 1.9 and 1.912 Å resolution with 6% input information. The OASIS phases were fed to ARP/wARP for automatic model building and the structure determination was completed using REFMAC5.
KeyWords: ACORN, OASIS, model-building, alkaline cellulaseapo form, cytokine.
How to cite: S. Selvanayagam et. al. ACORN with OASIS as a High Throughput Tool for Macromolecular Structure Determination. Int J Comput Bioinfo In Silico Model. 4(2) 2015: 629-634
ABSTRACT: Vitiligo is a skin disorder based on auto-immune mediated destruction of melanocytes causing depigmentation of skin at various areas of the human body. The mechanism of destruction is involved of multiple number of gene-gene interactions. Previously from the Genome-wide associated studies (GWAS), many number of genes involved in causing vitiligo are identified. But some of them are reported to be false-positives. In the current study, we made an attempt to identify some of the critical genes involved in causing vitiligo and the information from KEGG pathways/maps are employed to reconstruct a biochemical network/pathway using CellDesigner v4.4 software. The cross talks of the genes in various vital pathways leading to distinct cellular functions are understood by considering the unique/common genes associated in various pathways. The most necessitated pathways of vitiligo disease network are wnt signaling, MAPK signaling, calcium signaling, JAK-STAT signaling, T-cell receptor signaling, etc. Considering some of the gene sets in the signaling pathways the common topology of the interaction network are identified. For the same gene sets, the functional protein interaction partners are also predicted using STRING protein interaction database to identify the highly active hubs and their topologies which facilitates in emphasizing the network biology of vitiligo disease.
KeyWords: Biochemical network, Cell designer, Genetic disorder, Protein-Protein interaction, Signaling pathways and Vitiligo.
How to cite: Krishna Chaitanya et. al. Identifying the Critical Hub Topologies in Vitiligo Disease Network by Biochemical Pathway Reconstruction and Protein Interaction Partners Prediction. Int J Comput Bioinfo In Silico Model. 4(2) 2015: 635-642
ABSTRACT: The hemochromatosis gene (HFE) is located on chromosome 6 in close proximity to HLA-A gene. HFE is a cell surface membrane protein; its function involved in iron homeostasis and directly regulates iron absorption. Defects of HLA-H (HFE) gene cause the majority cases of inherited haemochromatosis (HFE haemochromatosis -HC-). Identifying SNPs responsible for specific phenotypes appears to be problem that is very difficult to solve, and to overcome this problem of testing overwhelming numbers of SNPs (single nucleotide polymorphisms), would be priorities SNPs according to their functional significance. Bioinformatics help to discriminate between neutral and deleterious SNPs, which constitute the majority of genetic variation and SNPs of likely functional importance. The objective of the present study was to identify deleterious SNPs within (SNP database) located in coding-nonsynonymous, 3 untranslated regions and promoter regions of HLA-H gene. In this study many international databases such as (NCBI, Uniprot, PolymiRTS) were used to identify functional SNPs within (SNPs database -dbSNP-) located in coding-nonsynonymous, 3-untranslated region and promoter regions of HLA-H gene, in addition nsSNPs were analyzed using bioinformatics tools (SIFT, PolyPhen, I-mutant, CPH, Chimera). Analysis results were as follow, two new functional (pathological) nonsynonymous SNPs (M35T) and (T17I) had been detected, which may disrupt the protein function conformation, also in 3′UTR, 18 functionally SNPs disrupts a conserved of 52 miRNA site, and creates a new binding site of 41 miRNA. Furthermore nil SNP were found within predicted promoter regions. In conclude, these new SNPs can thus be used for diagnostic test as add to hemochromatosis (HH) SNPs profile, which might play an important role in investigation of disorder that results from excess of total body iron.
KeyWords: Single-nucleotide polymorphisms (SNPs), hereditary hemochromatosis, HLA-H or HFE, insilico analysis, nonsynonymous SNPs (nsSNPs).
How to cite: Areej A. Khalfalla et. al. Novel deleterious nonsynonymous SNPs within HLA-H (HFE) gene can be used as diagnostic marker to predict hereditary Hemochromatosis: Using bioinformatics analysis. Int J Comput Bioinfo In Silico Model. 4(2) 2015: 643-650