International Journal of Computational Bioinformatics and In Silico Modeling
ABSTRACT: Fat mass and obesity associated gene has shown a strong association with adiposity in children and adults during several Genome Wide Association studies. It encodes an enzyme which catalyzes demethylation of single stranded DNA by using 2-oxoglutarate (2-OG) as a co-substrate. A mutation in the N - terminal of the enzyme encodes a glutamine in place of the arginine residue at position 322, which results in a complete disruption of protein function. Sequence analysis Arg322 is a highly conserved amino acid in the Fat mass obesity associated protein in animals. Homology modeling analysis reveals that 2-OG binding site of the enzyme which comprises various amino acids including Arg322. Molecular docking studies showed that Gln322 was unable to develop the hydrogen bonding and electrostatic interaction with the 2-OG. These interactions are important for extending the 2-OG to make its bonds more accessible to other amino acids. This study indicates that Arg322 is one of the most conserved amino acid in FTO protein which is directly involved in the catalysis of the 2-OG to succinate and CO2.
KeyWords: Fat mass obesity associated protein, 2-oxoglutarate, homology modeling, molecular docking, loss of function mutation.
How to cite: Mazhar Hussain et. al. Structural Characterization of Arg322Gln Mutation in Fat Mass and Obesity Associated Protein. Int J Comput Bioinfo In Silico Model. 3(5) 2014: 466-472
ABSTRACT: Homology modeling and structural analysis of human N-acetyl-alpha-neuraminidase 3 (NEU3) were performed with a software package the Molecular Operating Environment. A human NEU2 (PDB code: 1SNT) was selected as a template for the 3D structure modeling of NEU3. The modeled NEU3 showed significant 2D and 3D similarities to NEU2. The contact energy profiles of the NEU3 model were in good agreement with those of the NEU2 structure. Ramachandran plots revealed that only 2.5% of the amino acid residues were in the disfavored region for NEU3. These results indicate that the NEU3 model was successfully modeled and analyzed. To the best of my knowledge, this is the first report of NEU3 model with detailed analyses, and the data verify that the model can be utilized for application to target NEU3 for the development of anticancer drugs.
KeyWords: N-acetyl-alpha-neuraminidase 3 (NEU3), cancer, in silico
How to cite: Hideaki Yamaguchi. Homology modeling and structural analysis of human N-acetyl-alpha-neuraminidase 3 (NEU3). Int J Comput Bioinfo In Silico Model. 3(5) 2014: 473-478
ABSTRACT: Kruppel like factors (KLFs) are highly related zinc-finger proteins that are important components of the eukaryotic cellular transcriptional machinery. It is expressed in the nucleus of many cell types and its expression is elevated in several human cancers. KLF8 expression is increased in several types of human cancer cells and tissues, and ectopic expression of KLF8 induces transformation. The encoded protein is thought to play an important role in the regulation of epithelial to mesenchymal transition, a process which occurs normally during development but also during metastasis. In this study previously modelled structure was used for Docking and finding best binding ligand in the protein and that can alter the factions of KLF8 protein. For this purpose, a virtually screened 3D model of KLF8 was explored. The unliganded KLF8 was docked and best five docking solutions complex were selected and analyzed by Ligplot (http://www.ebi.ac.uk/thrnto-srv/software/LIGPLOT/). The analysis showed that Dasatinib, Doxorubicin, Pazopanib, Sorafenib & SU 6656 has maximum potential against unliganded protein. The analysis was done on the basis of scoring and binding ability and Dasatinib indicated minimum energy score and highest number of interactions with active site residue and could be a promising inhibitor for KLF8 as Drug target.
KeyWords: KLF8, Metastasis, NIH3T3, Docking, Ligplot
How to cite: Renukesh Verma et al. Computer-aided Screening of Therapeutic Ligands against KLF8 Protein (Homo sapiens). Int J Comput Bioinfo In Silico Model. 3(5) 2014: 479-482
ABSTRACT: Kappa casein protein belong to phosphoprotein’s casein family which contribute 80% of milk protein comprise of αS1, αS2, β-casein and κ-casein. Kappa casein gene (CNS3) is highly conserved in mammalian species and show variation containing 1997 base pairs. Kappa-casein involved in vital physiological processes. Along with the stabilizing coagulum by interfering with lactation cycle, it has many antimicrobial activities against Escherichia, Helicobacter pylori, Listeria, Salmonella and Staphylococcus, yeast and filamentous fungi. To date the X-ray structure of Kappa casein is not available. The sequence under accession no of P79139 was retrieved from uniprot and 3D structure was built with template ATP-dependent RNA helicase p47 (PDB ID 1XTI.A) showing 43.4% sequence identity using MOE2010.11. The alignment of target and template protein was done using MUSCLE server. The structure was refined by subjecting to MOE-DYNAMIC tool and final structure was used for protein-protein interaction with Helicobacter pylori (data not shown).The consistency of modeled structure was confirmed by getting acceptable scoring from ERRAT and Rampage owing to high accuracy of MOE for modeling and dynamics simulation. Toward the inhibitory activity this modeled structure may unclose the mechanism of eradication of helicobacter pylori from gastric epithelial cell.
KeyWords: Homology modeling, Md simulation, Casein and Inhibitor
How to cite: Abdul Wadood et al. Structural Modeling and Molecular Dynamics Simulation Studies of Camel Milk Kappa Casein Protein. Int J Comput Bioinfo In Silico Model. 3(5) 2014: 483-490
ABSTRACT: Methods of identification of the effective causes (Masalik al-Illa') are based on inductive logic and analogy (Qiyas), which means that the search can be particular rather than universal. Qiyas, however, takes place through comparison between the qualities of two different parts. This study introduces these paths and shows the experimental scientific rules on which they depend. Besides, light is shed on the degree of the appropriateness of these paths to the issues of jurisprudence and their degrees of certainty. These methods have been used in experimental sciences among Muslims in the Middle Ages, also contributed to the development of modern of new scientific methods for modeling.
KeyWords: identification, logic
How to cite: Sobhi Rayan. Methods of Effective Causes. Int J Comput Bioinfo In Silico Model. 3(5) 2014: 491-496
ABSTRACT: Shigellosis is a most common disease of developing to industrialized countries with its most spreadable, contractable agent Shigella flexneri. It uses type three secretion system for invasion composed of a needle, and a needle tip protein ipaD which is responsible for the proper translocation of ipaB/ipaC complex forming a pore on the host cell membrane, causing host cell apoptosis. The ipaD is a potential drug target for shigellosis; this study has carried out by fixed-protein flexible-ligand based screening for inhibitor design. Protein model was built using Modeller and mutual interaction between protein and ligand was evaluated using AutoDockVina. Five potential ligands analyzed for each of the three active site of this needle-tip protein. Analyzing the binding energy, physicochemical properties and interaction pattern, ZINC13298260 and ZINC34037183 are considerably two good inhibitors. This theorized study proposes these ligands as potential therapeutics against shigellosis.
KeyWords: TTSS; ipaD; homology modeling; fixed-protein flexible ligand docking; docking
How to cite: Alam Md. Jahangir and Roy Tithi. In Silico Screening for Novel Inhibitors of Invasion Protein Antigen IpaD of Shigella flexneri - an agent of Shigellosis. Int J Comput Bioinfo In Silico Model. 3(5) 2014: 497-501
ABSTRACT: Single-nucleotide polymorphisms (SNPs) play a major role in the understanding of the genetic basis of many complex human diseases. Also, the genetics of human phenotype variation could be understood by knowing the functions of these SNPs owing to the importance of FANCA gene in a post replication repair or a cell cycle checkpoint function. In this work, we have analyzed the genetic variation that can alter the expression and the function of the FANCA gene using computational methods. Genomic analysis of FANCA was initiated Polyphen and SIFT server used to retrieve 16 harmful mutations, among of these 16 nsSNPs damaged SNPs five non-synonymous SNPs showed very damaging by higher PSIC score of the Polyphen server with a SIFT tolerance index of 0.00-0.01 (R318M, I493T, A610T, P739L, R1117G). Protein structural analysis with these amino acid variants was performed by using I-Mutant and Modeling amino acid substitution with chimera software to check their stability and the effect of the native and mutant residues protein and structure for all 16 nsSNPs damaged. Screening for these SNPs variants in coding region may be useful for Fanconi anemia disease molecular diagnosis. Of the total 229 SNPs in 3′UTR region of FANCA gene, 24 SNPs were found in the 3′ UTR contain alleles can be disrupts a conserved miRNA site, therefore might change the protein expression levels.
KeyWords: Single-nucleotide polymorphisms (SNPs), of FANCA gene, miRNA site, 3′UTR, Polyphen and SIFT
How to cite: Abubaker H. Mohamed et al. In Silico analysis of Single Nucleotide Polymorphisms (SNPs) in human FANCA gene. Int J Comput Bioinfo In Silico Model. 3(5) 2014: 502-513