Bioinformation

Malaria remains a global public health burden with significant mortality and morbidity. Despite the several approved drugs available for its management, the parasite has developed resistance to virtually all known antimalarial drugs. The development of a new drug that can combat resistant to Artemisinin based Combination Therapies (ACTs) for malaria is imperative. Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH), a flavin-dependent mitochondrial enzyme is vital in the parasite's pyrimidine biosynthesis is a well-known drug target. Therefore, it is of interest to document the MOLECULAR DOCKING analysis (using Maestro, Schrodinger) data of DIHYDROOROTATE DEHYDROGENASE PfDHODH from P. falciparum towards the design of effective inhibitors. The molecular docking features of 10 compounds with reference to chloroquine with PfDHODH are documented in this report for further consideration.

Diabetes mellitus is a metabolic disorder caused due to insulin deficiency. Banana flower is a rich source of flavonoids that exhibit anti diabetic activity. Insulin receptor is a tetramer that belongs to a family of receptor tyrosine kinases. It contains two alpha subunits that form the extracellular domain and two beta subunits that constitute the intracellular tyrosine kinase domain. Insulin binds to the extracellular region of the receptor and causes conformational changes that lead to the activation of the tyrosine kinase. This leads to autophosphorylation, a step that is crucial in insulin signaling pathway. Hence, compounds that augment insulin receptor tyrosine kinase activity would be useful in the treatment of diabetes mellitus. The 3D structure of IR tyrosine kinase was obtained from PDB database. The list of flavonoids found in banana flower was obtained from USDA database. The structures of the flavonoids were obtained from NCBI Pubchem. Docking analysis of the flavonoids was performed using Autodock 4.0 and Autodock Vina. The results indicate that few of the flavonoids may be potential activators of IR tyrosine kinase.

Reliable identification of cis regulatory elements influencing transcription remains a challenging problem in molecular bioinformatics. This is especially true for enhancer elements which are often located hundreds of kilobases from the gene promoter. High resolution DNase hypersensitivity and connectivity profiling by the ENCODE consortium provides evidence of millions of interacting cis-acting elements in the human genome. This prior knowledge can be incorporated into genome-wide expression analyses, in the form of gene sets sharing regulatory sequence motifs in known DNase hypersensitivity peak regions. High proportions of enrichment among the most extreme differentially transcribed genes from controlled biological experiments may suggest novel hypotheses about signalling pathways. The utility of this approach is demonstrated with the reanalysis of a microarray-derived gene expression data set through the Gene Set Enrichment Analysis pipeline, uncovering new putative distal cis e...

This study describes the physical stability and optimization of nutrient components for an extracellular protease produced by Bacillus strains isolated from fruits and vegetable waste, Lucknow, India. The isolated proteases could hydrolyze various native proteinaceous substrates such as bovine serum albumin, casein, skim milk, but not the gelatin. The strain JX416854 and isolate 10 yielded maximum protease (831; 703 U/ml) under optimized conditions: Nutrient, Casein broth; pH 7.0; shaking condition 37°C for 36 h. Crude protease exhibited activity over a wide range of pH (6.0-10.0) and found to be stable at (10-70°C), pH stable at 7- 9.0. The significant protease activity was observed with divalent cations Ca2+ and Mg2+ and EDTA. Further, significant blood destaining properties and stabilities with detergents were also observed. Thus, the significant potency and stability of these enzymes indicated their industrial importance and could be an alternative protease for various industria...

The β-lactamases enzymes cleave the amide bond in β-lactam ring, rendering β-lactam antibiotics harmless to bacteria. In this communication we have studied structure-function relationship and phylogenies of class A, B and D beta-lactamases using structure-based sequence alignment and phylip programs respectively. The data of structure-based sequence alignment suggests that in different isolates of TEM-1, mutations did not occur at or near sequence motifs. Since deletions are reported to be lethal to structure and function of enzyme. Therefore, in these variants antibiotic hydrolysis profile and specificity will be affected. The alignment data of class A enzyme SHV-1, CTX-M-15, class D enzyme, OXA-10, and class B enzyme VIM-2 and SIM-1 show sequence motifs along with other part of polypeptide are essentially conserved. These results imply that conformations of betalactamases are close to native state and possess normal hydrolytic activities towards beta-lactam antibiotics. However, c...

Endophytic bacteria are harmless in most plant species; and known to boost the growth and development of the host plants probably by secreting growth hormones. The isolation, identification and screening of endophytic bacteria for the plant growth regulators like cytokinin are needed to get the leads for their applications in agriculture sector. We describe the isolation and identification of the bacterial endophytes from the leaves of Sambung Nyawa [Gynura procumbens (Lour.) Merr.] and their screening for cytokinin-like compounds. We isolated three endophytic bacteria from the leaves of G. procumbens collected from the forest research institute of Malaysia (FRIM). They were further identified using amplified 16S rRNA gene sequence based method of bacterial identification. The ethyl acetate extracts of the isolates-broth were analyzed using cucumber cotyledon greening bioassay (CCGB) to determine the presence of cytokinin-like compounds. Consequently, the bacterial putative endophyt...

Leishmaniasis is one of the most neglected diseases with high morbidity and mortality rate. Severe side effects with existing drug and lack of proper vaccine encouraged us to design alternative models to combat the disease. We showed that PP1 of Leishmania donovani mediates immunomodulation in host macrophages needed for parasite survival. Therefore, it is of interest to report the molecular docking analysis of 512 isoflavone derivatives with the phosphatase 1 protein from Leishmania donovani to highlight compound 362 (5-hydroxy-5-{9-[2-methoxy-2-(2-methylfuran-3-yl) ethyl]-1H,3H,4H,10bH-pyrano[4,3-c]chromen-3-yl}pentanoic acid) having good binding features and acceptable ADMET properties for further consideration.

Natural products are important sources of drug discovery. In this context groups of different set of phytochemicals were taken and docked into the different cavities of the Reverse transcriptase (PDB ID: 1REV) of Human immunodeficiency virus (HIV) and results were discussed. Natural compounds such as Curcumin, Geranin, Gallotannin, Tiliroside, Kaempferol-3-o-glucoside and Trachelogenin were found to very effective according to its binding energy and ligand efficiency score. Those compounds also were found to have no adverse effect as carcinogenicity and mutagenicity and favorable drug likeness score. Hence, considering the facts those compounds could use effectively for HIV-1 drug discovery.

The leader gene approach is a data mining method based on the systematic search for genes involved in a specific process and their ranking according to the number of interconnections with the other genes identified. The genes with the strongest interconnections are termed leader genes, since they may be supposed to play an important role in the process. The potential of malignant progression of OLP to oral squamous cell carcinoma (OSCC) is still not completely clear. In this study, the leader gene approach is applied to investigate the association between OLP and OSCC at a molecular level. Results were integrated with those obtained in an experimental analysis (see paper 1 of this series). Genes involved in OLP and OSCC were identified by systematic queries to dedicated databases. Interconnections among identified genes were calculated and given a confidence value using STRING database. Leader genes were identified by clustering genes according to their interconnections. This theore...

A bacterial strain, designated AcBz01, was isolated from a water sample collected from Gomti River, Lucknow, India, and identified using a molecular approach. On the basis of the bacterial 16S rRNA gene sequence phylogeny and comparison of this gene sequence with sequences in Ribosomal Database project II, evidence given in this study, it is proposed that isolate is closely related to members of the genus Acinetobacter. Identification and annotation of regulatory elements in the 16S rRNA gene and characterization of their interaction with the respective transcription factor can provide basis for better understanding of the mechanism of network of gene interaction of functionally related genes. The identification of such sites is relevant for locating promoter boundary of a gene and it also allows the prediction of specific gene expression pattern and response to disturbances in a known signaling pathway. Computational identification of regulatory elements and Transcription Factor with their binding sites in 16S rRNA gene of Acinetobacter sp. was performed using BPROM tool. We predicted the regulatory elements are TSS, -10 box, -35 box and three Transcription Factor (narP, ompR and fadR) with their binding sites in the upstream region of 16S rRNA gene of Acinetobacter sp. AcBz01. The GenBank accession number for 16S rRNA gene of Acinetobacter sp. AcBz01 is {"type":"entrez-nucleotide","attrs":{"text":"EU931637","term_id":"197205391"}}EU931637.

Wheat is a vital dietary component for human health and widely consumed in the world. Wheat rusts are dangerous pathogens and contribute serious threat to its production. In present study, PCR-Based DNA Markers were employed to check the rust resistance genes among 20 wheat genotypes and 22 markers were amplified. NTSYS-pc 2.2 was used to calculate genetic diversity and Nei and Li's coefficients ranged from 0.55 to 0.95. Cluster analysis was obtained using UPGMA (Unweighted Pair Group Method of Arithmetic Average) algorithm. Maximum no. of genes (23) was amplified from TW-760010 genotype whereas minimum no of genes (14) were amplified from TW-76005 genotype. The data gained from present study open up new ways to produce new varieties by breeding rust resistant germplasm to avoid the economic and food loss and varieties with improved characteristics.

The HNH Database is a collection and sequence-based classification of HNH domain proteins. The database contains about 1913 HNH domain containing proteins, and is classified into 10 subsets based on the sequence pattern. Each of these subsets has unique signature sequences. We have shown a correlation between the subset combination and their domain association and function. Functional divergence of this domain may be due to the combination of these conserved patterns and the large variations in the non-conserved regions. HNHDb is freely available at http://bicmku.in:8081/hnh.

Cotton leaf curl Allahabad virus (CLCuAV) belongs to genus Begomovirus, family Geminiviridae. It has single stranded monopartite DNA genome transmitted by whitefly (Bemisia tabaci). MicroRNAs (miRNAs) belong to class of endogeneous small RNAs which suppress expression of genes following cleavage or translational inhibition of target messenger RNAs. They are demonstrated to be involved in a number of plant processes such as, development, biotic and abiotic stresses. Employing in silico approach, high scoring miRNA-target pairs satisfying rules of minimum free energy and maximum complementarity were selected to investigate if they possess the potential to bind the genome CLCuAV. Our results revealed that miRNA species viz., ghr-miR2950 can target all the viral genes, ghr-miR408 targets overlapping transcripts of AC1 and AC2 genes; while ghr-miR394 and ghr-miR395a and miR395d could bind overlapping transcripts of AC1 and AC4 genes. This is the first report of prediction of cotton miRNA...

Methicillin resistant Staphylococcus aureus (MRSA), a pathogenic bacterium that causes life threatening outbreaks such as community-onset and nosocomial infections has emerged as ‘superbug’. The organism developed resistance to all classes of antibiotics including the best known Vancomycin (VRSA). Hence, there is a need to develop new therapeutic agents. This study mainly evaluates the potential use of botanicals against MRSA infections. Computer aided design is an initial platform to screen novel inhibitors and the data finds applications in drug development. The drug-likeness and efficiency of various herbal compounds were screened by ADMET and docking studies. The virulent factor of most of the MRSA associated infections are Penicillin Binding Protein 2A (PBP2A) and Panton-Valentine Leukocidin (PVL). Hence, native structures of these proteins (PDB: 1VQQ and 1T5R) were used as the drug targets. The docking studies revealed that the active component of Aloe vera, β-sitosterol (3S, 8S, 9S, 10R, 13R, 14S, 17R) ­17­ [(2R, 5R)-5-ethyl-6-methylheptan-2-yl] -10, 13-dimethyl 2, 3, 4, 7, 8, 9, 11, 12, 14, 15, 16, 17- dodecahydro-1H-cyclopenta [a] phenanthren-3-ol) showed best binding energies of -7.40 kcal/mol and ­6.34 kcal/mol for PBP2A and PVL toxin, respectively. Similarly, Meliantriol (1S-1-[ (2R, 3R, 5R)-5-hydroxy-3-[(3S, 5R, 9R, 10R, 13S, 14S, 17S)-3-hydroxy 4, 4, 10, 13, 14-pentamethyl-2, 3, 5, 6, 9, 11, 12, 15, 16, 17-decahydro-1H-cyclopenta[a] phenanthren-17-yl] oxolan-2-yl] -2- methylpropane-1, 2 diol), active compound in Azadirachta indica (Neem) showed the binding energies of ­6.02 kcal/mol for PBP2A and ­8.94 for PVL toxin. Similar studies were conducted with selected herbal compound based on pharmacokinetic properties. All in silico data tested in vitro concluded that herbal extracts of Aloe-vera, Neem, Guava (Psidium guajava), Pomegranate (Punica granatum) and tea (Camellia sinensis) can be used as therapeutics against MRSA infections.

Periodontitis have been referred to as the sixth complication of diabetes found in high prevalence among diabetic patients than among healthy controls. The aim of the present study was to examine the periodontal disease status among collected dental plaque samples. Chromosomal DNA was isolated and amplified by universal primers. The DNA was sequenced for bacterial confirmation and phylogenetic analysis performed for the evolutionary relationship with other known pathogens. No amplification products were observed in groups labeled non periodontal and non Diabetes (NP&ND) and non Periodontal and Diabetes (NP&D). But in the case of Periodontal and non Diabetes (P&ND) groups 22 amplified products were observed. In case of Periodontal and Diabetes (P&D), 32 amplified products were positive for microbes. Among the four microbial groups, Treponemadenticola, and Tannerella forsythia were found to be prevalent in P&D. The phylogenetic analysis of 16s rRNA of Treponemadenticola showed the rel...

Cytochrome P450 mono-oxygenases (2UUQ) enzyme from Mycobacterium tuberculosis catalyzes oxidation of organic compounds such as lipids and steroidal hormones therefore remain as potential drug target. Currently available first line anti-tuberculosis drugs have been caused several side effects in the body as well as resistance development by mycobacterium against these drugs, necessitates the considerable need for finding new drugs. Therefore, we propose a structure based computational method to find a new potential inhibitor for cytochrome P450 mono-oxygenases enzyme. Compounds from several ligand databases were docked against the functional sites of 2UUQ (A) through the standard GEMDOCK v2.0 and AUTODOCK4.0 molecular docking tools. Commercially available chemical compound ZINC00004165 (5-[3-(2-nitroimidazol-1-yl) propyl] phenanthridine) has produced top rank with lowest interaction energy of -113.2 (via GEMDOCK) and lowest docking energy of -9.80 kcal/mol (via AUTODOCK) as compared ...