fabp4 is central to eight obesity associated genes: a functional gene network-based polymorphic study.

Network study on genes and proteins offers functional basics of the complexity of gene and protein, and its interacting partners. The gene fatty acid-binding protein 4 (fabp4) is found to be highly expressed in adipose tissue, and is one of the most abundant proteins in mature adipocytes. Our investigations on functional modules of fabp4 provide useful information on the functional genes interacting with fabp4, their biochemical properties and their regulatory functions. The present study shows that there are eight set of candidate genes: acp1, ext2, insr, lipe, ostf1, sncg, usp15, and vim that are strongly and functionally linked up with fabp4. Gene ontological analysis of network modules of fabp4 provides an explicit idea on the functional aspect of fabp4 and its interacting nodes. The hierarchal mapping on gene ontology indicates gene specific processes and functions as well as their compartmentalization in tissues. The fabp4 along with its interacting genes are involved in lipid metabolic activity and are integrated in multi-cellular processes of tissues and organs. They also have important protein/enzyme binding activity. Our study elucidated disease-associated nsSNP prediction for fabp4 and it is interesting to note that there are four rsID׳s (rs1051231, rs3204631, rs140925685 and rs141169989) with disease allelic variation (T104P, T126P, G27D and G90V respectively). On the whole, our gene network analysis presents a clear insight about the interactions and functions associated with fabp4 gene network.

Revealing the Strong Functional Association of adipor2 and cdh13 with adipoq: A Gene Network Study.

In the present study, we have analyzed functional gene interactions of adiponectin gene (adipoq). The key role of adipoq is in regulating energy homeostasis and it functions as a novel signaling molecule for adipose tissue. Modules of highly inter-connected genes in disease-specific adipoq network are derived by integrating gene function and protein interaction data. Among twenty genes in adipoq web, adipoq is effectively conjoined with two genes: Adiponectin receptor 2 (adipor2) and cadherin 13 (cdh13). The functional analysis is done via ontological briefing and candidate disease identification. We observed that the highly efficient-interlinked genes connected with adipoq are adipor2 and cdh13. Interestingly, the ontological aspect of adipor2 and cdh13 in the adipoq network reveal the fact that adipoq and adipor2 are involved mostly in glucose and lipid metabolic processes. The gene cdh13 indulge in cell adhesion process with adipoq and adipor2. Our computational gene web analysis also predicts potential candidate disease recognition, thus indicating the involvement of adipoq, adipor2, and cdh13 with not only with obesity but also with breast cancer, leukemia, renal cancer, lung cancer, and cervical cancer. The current study provides researchers a comprehensible layout of adipoq network, its functional strategies and candidate disease approach associated with adipoq network.

Gene and Protein Network Analysis of AmpC ß Lactamase.

AmpC ß-lactamase is a cephalosporinase, which exhibits resistance against all existing ß-lactam antibiotics except carbapenems. Their occurrence in many bacterial pathogens poses a threat to public health and is a growing concern in the medical world. The ampC gene is highly inducible in the presence of ß-lactam antibiotics and can be expressed in high levels due to mutation. This inducible expression is regulated by several functional genes. Several studies on functional relationship of these genes and its resistance mechanisms are carried out but it still lacks comprehensible evidences. Thus, in our current study, we used computational gene networks to analyze ampC gene. Based on its interaction type, co-expression, Gene Ontology, and text mining, a functional interaction network is constructed. Around 247 functional genes in 15 different bacterial genus have a functional association with ampC gene. It is predicted that 19.8% ampD, 13.3% frdD, 8.5% gcvA, 2.4% ampR, and 55.7% of other functional partners are associated with ampC gene. Our present study provides a glimpse about the functional gene network of ampC gene and also provides the integrated evidence for ampC gene in regulating the ß-lactamase production and its role in antibiotic resistance.

In silico study on Penicillin derivatives and Cephalosporins for upper respiratory tract bacterial pathogens.

Upper respiratory tract infection (URTI) is an acute infection which involves the upper respiratory tract: nose, sinuses, tonsils and pharynx. URT infections are caused mainly by pathogenic bacteria like Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus. Conventionally, ß-lactam antibiotics are used to treat URT infections. Penicillin binding proteins (PBPs) catalyze the cell wall synthesis in bacteria. ß-Lactam antibiotics like Penicillin, Cephalosporins, Carbapenems and Monobactams inhibit bacterial cell wall synthesis by binding with PBPs. Pathogenic bacteria have efficiently evolved to resist these ß-lactam antibiotics. New generation antibiotics are capable of inhibiting the action of PBP due to its new and peculiar structure. New generation antibiotics and Penicillin derivatives are selected in this study and virtually compared on the basis of interaction studies. 3-Dimensional (3D) interaction studies between Lactivicin, Cefuroxime, Cefadroxil, Ceftaroline, Ceftobiprole and Penicillin derivatives with PBPs of the above-mentioned bacteria are carried out. The aim of this study was to suggest a potent new generation molecule for further modification to increase the efficacy of the drug for the URTI.

Flavonoid from Carica papaya inhibits NS2B-NS3 protease and prevents Dengue 2 viral assembly.

UNLABELLED: Dengue virus belongs to the virus family Flaviviridae. Dengue hemorrhagic disease caused by dengue virus is a public health problem worldwide. The viral non structural 2B and 3 (NS2B-NS3) protease complex is crucial for virus replication and hence, it is considered to be a good anti-viral target. Leaf extracts from Carica papaya is generally prescribed for patients with dengue fever, but there are no scientific evidences for its anti-dengue activity; hence we intended to investigate the anti-viral activity of compounds present in the leaves of Carica papaya against dengue 2 virus (DENV-2). We analysed the anti-dengue activities of the extracts from Carica papaya by using bioinformatics tools. Interestingly, we find the flavonoid quercetin with highest binding energy against NS2B-NS3 protease which is evident by the formation of six hydrogen bonds with the amino acid residues at the binding site of the receptor. Our results suggest that the flavonoids from Carica papaya have significant anti-dengue activities. ABBREVIATIONS: ADME - Absorption, distribution, metabolism and excretion, BBB - Blood brain barrier, CYP - Cytochrome P450, DENV - - Dengue virus, DHF - Dengue hemorrhagic fever, DSS - Dengue shock syndrome, GCMS - - Gas chromatography- Mass spectrometry, MOLCAD - Molecular Computer Aided Design, NS - Non structural, PDB - Protein data bank, PMF - Potential Mean Force.

Aromatic-aromatic interactions: analysis of π-π interactions in interleukins and TNF proteins.

Aromatic-aromatic hydrogen bonds are important in many areas of chemistry, biology and materials science. In this study we have analyzed the roles played by the π-π interactions in interleukins (ILs) and tumor necrosis factor (TNF) proteins. Majority of π-π interacting residues are conserved in ILs and TNF proteins. The accessible surface area calculations in these proteins reveal that these interactions might be important in stabilizing the inner core regions of these proteins. In addition to π-π interactions, the aromatic residues also form π-networks in ILs and TNF proteins. The results obtained in the present study indicate that π-π interactions and π-π networks play important roles in the structural stability of ILs and TNF proteins.

Leucine to proline substitution by SNP at position 197 in Caspase-9 gene expression leads to neuroblastoma: a bioinformatics analysis.

To understand the role of CASP9 (Caspase-9) gene products in relation to neuroblastoma disease, we have analyzed the single nucleotide polymorphisms (SNPs) associated with this gene. This can help us understand the genetic variations that can alter the function of the gene products. A total of 941 SNPs are investigated for CASP9 gene. To determine whether a non-synonymous SNP (nsSNP) in this gene affects its protein product, we used certain computational tools which predicted one nsSNP, rs1052574, to have deleterious phenotypic effect. This polymorphic variant results in amino acid substitution from leucine to proline at 197 position, i.e., from acyclic amino acid to a 5-membered amino acid which resides in the buried area of the protein with a high level of conservation. This amino acid substitution shows a transition from helix to coil in the mutant protein. Hence, due to the complete alteration in the structural property of the amino acid side chain, the stability of the protein is reduced which may affect the function of CASP9 protein, leading to deregulation of apoptosis and neuroblastoma development.

Arginine and Lysine interactions with π residues in metalloproteins.

Metalloproteins have many different functions in cells such as enzymes; signal transduction, transport and storage proteins. About one third of all proteins require metals to carry out their functions. In the present study we have analyzed the roles played by Arg and Lys (cationic side chains) interactions with π (Phe, Tyr or Trp) residues and their role in the structural stability of metalloproteins. These interactions might play an important role in the global conformational stability in metalloproteins. In spite of its lower natural occurrence (1.76%) the number of Trp residues involved in energetically significant interactions is higher in metalloproteins.