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Molecular modeling and docking studies of glutamate racemase in Vibrio vulnificus CMCP6

Natarajan Vidya, Bagavathkumar Vadivukkarasi*, Gopalakrishnan Manivannan and Krishnan Anbarasu

Department of Bioinformatics, HelixInfoSystems, 132A, II Floor,Sterling Towers, IV Cross Street, Sterling Road,
Chennai-600034, India

Corresponding author

Edited by H. Michael; received June 16, 2008; revised and accepted August 22, 2008; published October 11, 2008
Journal name: In Silico Biology 8, 0036 (2008); ©2008, Bioinformation Systems e.v.

Identification of novel drug targets in silico in Vibrio vulnificus is important as it is one of the emerging pathogenic microorganisms. Glutamate racemase, an important constituent of bacterial cell wall is chosen for structure prediction using homology modeling. With the aid of tools and
softwares like MODELLER and Swiss-PdbViewer, the 3D structure is predicted and the final model is refined by energy minimization. The quality of the refined model is assessed using PROCHECK. The interaction between the predicted structure of glutamate racemase and its potential inhibitors namely L-serine O-sulfate, (2R,4R)-2-amino-4-(2-benzo[b]thienyl)methyl pentanedioic acid, aziridino glutamate, exiguaquinol, γ-2 naphthylmethyl-D-glutamate and D-glutamine is analysed in silico by Autodock. The results indicate that certain residues like Asp13, Tyr45, Gly46, Asn78, Thr79, Cys185, His187 are highly conserved across the active site stretches of different bacterial species and may possibly assume precedence over the other residues for inhibitory action. This study provides an insight into the structure of glutamate racemase in V. vulnificus and also gives an idea about potential sites responsible for inhibitory action that could further be substantiated by experimental investigations.

Stem cell with their ability to turn virtually into any cell type in the body have inspired a revolutionary breakthrough in the field of medicine .stem cell research using an external source is always encumbered by, serious ethical issues and immunological side effects. Auto stem cell therapy is the need of the hour. This involves the natural renewal of the body by self adult stem cells. Flavonoids are one of the biologically active chemical constituents of plants. These natural products are readily available to man in the form of Vegetables and fruits. When these are supplied through diet, they trigger auto stem cell therapy. SH2 containing Inositol Phosphatase I and II is the key enzymes which play a vital role in the development of Hematopoietic stem cells, a type of adult stem cells. This study involves an Insilico approach to analyze the activation of SHIP enzyme by Flavonoids by vegetable sources. Bioinformatics method are mainly harnessed to reduce the time, cost and risk associated with drug discovery. Docking scores, dynamic studies and toxicity test results indicate the application of dietary Flavonoids as natural potential and safe therapeutic agents to prevent and combat blood related diseases, by supporting self Hematopoietic stem cell development.

In the battle for a disease free world, focus is laid more on synthetic compounds as drugs without even bothering about the harmful side effects they produce. This study is a novel approach emphasizing the significance of natural products as a prime solution to unanswered questions like the treatment of the 'Silent Killer'-"Polycystic Kidney Disease" (PKD). Flavonoids are one of the biologically active chemical constituents of plants. These natural products are readily available to man in the form of vegetables and fruits. The emergence of Bioinformatics has provided a platform to explore diseases at the molecular level using Computational techniques. Insilico methods are mainly harnessed to reduce the time, cost and risk associated with Drug Discovery. The key protein namely Cystic Fibrosis Transmembrane conductance Regulator which upon mutation plays major roles in cyst formation, fluid accumulation and hypertension in PKD is selected as drug target. The 3D structure is mutated and subjected to Molecular Docking with flavonoids from vegetable sources. Docking scores and Insilico Toxicity test result indicates the application of Flavonoids as Potential and Natural Therapeutic agents to combat PKD.

Green tea is tea made solely with the leaves of Camellia sinensis that have undergone minimal oxidation during processing. Green tea drinkers have lower chances of developing certain types of cancer. Green tea contains salubrious polyphenols, particularly catechins, the most abundant of which is epigallocatechin gallate. Epigallocatechin gallate (EGCG), also known as Epigallocatechin 3-gallate, is the ester of epigallocatechin and gallic acid, and is a type of catechin. EGCG is the most abundant catechin in most notably tea, among other plants, and is also a potent antioxidant that may have therapeutic properties for many disorders including cancer. There is increasing evidence to show that EGCG – along with other flavonoids – can be beneficial in treating brain, prostate, cervical and bladder cancers.

DCHC513MI is a Chinese Herbal Compounds database, contains the informations about their Molecular interactions with the diseased protein determined using various Bioinformatics tools. Users can perform simple and advanced searches based on annotations relating to Herbal compunds and their medicinal values

Snake venoms are rich in protein and peptide toxins that have specificity for a wide range of tissue receptors, making them clinically challenging and scientifically fascinating, especially for drug design and finding novel drug targets. Availability of sequences and structure of toxin protein has provided a tremendous amount of information that can be useful in drug target identification. Estimates put the number at 2.5 million snake bites per year, resulting in perhaps 125,000 deaths but present day antidotes in form of immunoglobulin antivenoms or animal hyperimmune globulin is not readily available and highly expensive. In this study I have found out novel drug targets through bioinformatics approach from plant phytochemicals of VISHAKALLU constituents practiced by Kaani tribes of Tirunelveli, South India who follows Siddha system of medicine (SSM) is one of the oldest traditional systems of medicine. Based on a subtractive genomic approach, in which the subtraction data set between the host and venom proteins provide information for a set of genes that are likely to be essential to the venom protein but absent in host. These set of procedure leads us to predict three dimensional structure of the protein. Based on the availability of the inhibitors from vishakallu, the predicted three dimensional structures were docked.

Pten protein plays an important role in cell signaling pathway. Mutation in this pten protein leads to various disease such as many type of cancers. The mutated structure of this pten protein is modeled using modeler 9v7.Molecular dynamics is the science of simulating the motions of a system of particles—applied to biological macromolecules gives the fluctuations in the relative positions of the atoms in a protein as a function of time. To calculate the free energy changes resulting from mutations in proteins we carried out molecular dynamics simulation of normal and mutated PTEN protein in an explicit water environment. The energy minimized mutated pten protein docking analysis with several inhibitors were carried out using AUTODOCK tool.

The objective of this work is to identify the Gene Expression analysis of Squamous cell lung cancer, a major type of non-small lung cancer. Although alterations of several genes, such as k- ras, c-myc, and p53, have been identified in a significant fraction of squamous cell lung cancer, none of these mutations are diagnostic of malignancy or predictive of tumor behavior over time. Here, we used oligonucleotide microarrays with probe sets complementary to >22,000 human genes to identify genes whose expression correlated with squamous cell lung cancer. Normal samples were readily distinguished from tumor samples, and the highly expressed tumour genes were further analysed. BRB array tool was used to calculate the upregulated genes in of squamous cell lung cancer gene expression dataset. Ontology-based networks were constructed based on the known squamous cell lung mechanism. After the extensive analysis with network, seven genes (Dsp, Ddr1, Psmb2, Ptprf, Hsp90B, Marcksl1, and Rad21) were identified as potential molecular markers for squamous cell lung cancer. The study highlights important molecular features of squamous cell lung cancer and identifies new genes as candidate molecular markers.