CARd-3D: Carbon Distribution in 3D Structure Program for Globular Proteins

Spatial arrangement of carbon in protein structure is analyzed here. Particularly, the carbon fractions around individual atoms arecompared. It is hoped that it follows the principle of 31.45% carbon around individual atoms. The results reveal that globularprotein''s atoms follow this principle. A comparative study on monomer versus dimer reveal that carbon is better distributed indimeric form than in its monomeric form. Similar study on solid versus liquid structures reveals that the liquid (NMR) structurehas better carbon distribution over the corresponding solid (X-Ray) structure. The carbon fraction distributions in fiber and toxinprotein are compared. Fiber proteins follow the principle of carbon fraction distribution. At the same time it has another broadspectrum of carbon distribution than in globular proteins. The toxin protein follows an abnormal carbon fraction distribution. Thecarbon fraction distribution plays an important role in deciding the structure and shape of proteins. It is hoped to help inunderstanding the protein folding and function.     

FAIR: A server for internal sequence repeats

An Internet computing server has been developed to identify all the occurrences of the internal sequence repeats in a protein and DNA sequences. Further, an option is provided for the users to check the occurrence(s) of the resultant sequence repeats in the other sequence and structure (Protein Data Bank) databases. The databases deployed in the proposed computing engine are up-to-date and thus the users will get the latest information available in the respective databases. The server is freely accessible over the World Wide Web (WWW). AVAILABILITY: http://bioserver1.physics.iisc.ernet.in/fair/     

Attenuation of NDEA‐induced hepatocarcinogenesis by naringenin in rats

Chemoprevention is one of the most promising and realistic approaches in the prevention of cancer. Several bioactive compounds present in fruits and vegetables have revealed their cancer curative potential on hepatocellular carcinoma. Naringenin is one such naturally occurring flavonoid widely found in citrus fruits. In this study, we examined the molecular mechanisms by which naringenin inhibited NDEA‐induced hepatocellular carcinoma in rats by analysing the expression patterns of proliferating cell nuclear antigen, Bcl‐2, NF‐κB, VEGF and MMP‐2/9. Enhanced cell proliferation and apoptotic evasion in NDEA‐induced hepatocarcinogenesis was associated with imbalance in pro‐apoptotic and anti‐apoptotic proteins together with upregulation of proliferating cell nuclear antigen (PCNA) and downregulation of caspase‐3. Administration of pretreatment and posttreatment of naringenin decreased the expression of PCNA and Bcl‐2 and increased the expression of Bax and caspase‐3, indicating antiproliferative and apoptotic effects, respectively. Administration of NDEA increased the tumour expression of NF‐κB, COX‐2, VEGF, MMP‐2 and MMP‐9 that was correlated with more aggressive lesions and tumour growth. Downregulation of NF‐κB, VEGF and MMPs by naringenin seen in the present study were correlated with the inhibition of liver tumour induced by NDEA. Our results suggest that naringenin could act as a legitimate agent by inhibiting cancer processes. Copyright © 2012 John Wiley & Sons, Ltd.     

Integrating Pathways of Parkinson's Disease in a Molecular Interaction Map

Parkinson's disease (PD) is a major neurodegenerative chronic disease, most likely caused by a complex interplay of genetic and environmental factors. Information on various aspects of PD pathogenesis is rapidly increasing and needs to be efficiently organized, so that the resulting data is available for exploration and analysis. Here we introduce a computationally tractable, comprehensive molecular interaction map of PD. This map integrates pathways implicated in PD pathogenesis such as synaptic and mitochondrial dysfunction, impaired protein degradation, alpha-synuclein pathobiology and neuroinflammation. We also present bioinformatics tools for the analysis, enrichment and annotation of the map, allowing the research community to open new avenues in PD research. The PD map is accessible at http://minerva.uni.lu/pd_map.     

Synthesis and α-glucosidase inhibition activity of dihydroxy pyrrolidines

A new series of Deacetylsarmentamide A and B derivatives, amides and sulfonamides of 3,4-dihydroxypyrrolidines as α-glucosidase inhibitors were designed and synthesized. The biological screening test against α-glucosidase showed that some of these compounds have the positive inhibitory activity against α-glucosidase. Saturated aliphatic amides were more potent than the olefinic amides. Among all the compounds, 5o/6o having polar –NH₂ group, 10f/11f having polar –OH group on phenyl ring displayed 3–4-fold more potent than the standard drugs. Acarbose, Voglibose and Miglitol were used as standard references. The promising compounds 6i, 5o, 6o, 10a, 11a, 10f and 11f have been identified. Molecular docking simulations were done for compounds to identify important binding modes responsible for inhibition activity of α-glucosidase.     

A combined computational-experimental analyses of selected metabolic enzymes in Pseudomonas species

Comparative genomic analysis has revolutionized our ability to predict the metabolic subsystems that occur in newly sequenced genomes, and to explore the functional roles of the set of genes within each subsystem. These computational predictions can considerably reduce the volume of experimental studies required to assess basic metabolic properties of multiple bacterial species. However, experimental validations are still required to resolve the apparent inconsistencies in the predictions by multiple resources. Here, we present combined computational-experimental analyses on eight completely sequenced Pseudomonas species. Comparative pathway analyses reveal that several pathways within the Pseudomonas species show high plasticity and versatility. Potential bypasses in 11 metabolic pathways were identified. We further confirmed the presence of the enzyme O-acetyl homoserine (thiol) lyase (EC: 2.5.1.49) in P. syringae pv. tomato that revealed inconsistent annotations in KEGG and in the recently published SYSTOMONAS database. These analyses connect and integrate systematic data generation, computational data interpretation, and experimental validation and represent a synergistic and powerful means for conducting biological research.     

Synthesis of some novel imidazole-based dicationic carbazolophanes as potential antibacterials

Synthesis of fluorescent imidazole-based dicationic carbazolophanes incorporating various spacer units is described. Interestingly, the cyclophanes 2a and 5a incorporating a pyridine moiety exhibited superior antibacterial activity against most of the pathogenic bacteria in the tested concentrations as compared to the other cyclophanes as well as the test control, benzalkonium chloride (BAC), cetylpyridinium chloride (CPC) and tetracycline.     

Role of thymine in protein coding frames of mRNA sequences

Distribution of thymine in protein coding mRNA sequences has been studied here. Our study suggest that thymine in protein coding sequences are not randomly distributed but with probability. Frame1 prefers to have definite amount of thymine. It is observed that the thymine content of frame 4 is also involved in protein coding. Frame 3 prefers to have least amount of thymine. However, frame 2 and frame 6 shows a variable degree of thymine content. The mRNA sequences of heterosexual animals, particularly, the human show a different distribution profile (less thymine in frame 1) compared to that of yeast and plants.