Bioinformatics

Cholinesterase inhibitors (ChE-Is) are the standard of therapy for treatment of patients with Alzheimer’s disease (AD) and are the only class of drugs approved by the Food and Drug Administration (FDA) for treatment of this condition. In this paper we used the new approach utilizing cheminformatics tools such as CORINA, Yet Another Scientific Artificial Reality Application (YASARA), and molecular docking program to identify binding affinity and mechanism of interaction between the ChE-Is with the target proteins. This approach should be helpful to understand the selectivity of the given drug molecule in the treatment of Alzheimer’s disease.

CME (continuing medical education) is a key concept of national strategies in health. A study was undertaken of the current knowledge and continuing future training requirements of nurses, Inspectors CME to inform policy to meet national goals of healthcare. Questionnaire distributed to nurses, pharmacist, doctors and health inspectors in rural hospital who practice Traditional Indian Medicine Technologies were used by 221% of respondents as part of their work-related activities. This paper describes health in India that increase provider and patient access to health information.

The aerobic gram positive bacterium Corynebacterium diphtheriae causes diphtheria, a respiratory tract illness characterized by symptoms such as sore throat, low fever, and an adherent membrane on the tonsils, pharynx, and/or nasal cavity. Therefore, it is important to develop preventive vaccines for diphtheria. The availability of the 2,488,635 bp long complete sequence for the C. diphtheriae genome provides an opportunity to understand cell mediated immune response using Computational Biology tools from the bacterial proteome sequence data. We selected 355 membrane proteins from the C. diphtheriae proteome using annotation data to identify potential HLA-DRB1 binding short peptide using modeling, simulations and predictions. This exercise identified 30 short peptides in membrane proteins showing binding capability to HLA-DRB1 alleles. These peptides serve as outline for the understanding of cell mediated immune response to C. diphtheriae. It should be noted that the predicted data to be verified using binding assays for further consideration.

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.

In drug discovery, the role of multiple receptors based therapeutics is found to be a highly critical approach in producing high efficacy with reduced side effects drug molecules. Hepatitis-C is found to be a threatful chronic disease, even ending up in death in many cases. In the present study, we have selected a few drugs which are found highly potent against Hepatitis-c and have studied their side effects. Understanding the source and hidden mechanisms of drug side effects is found to be challenging in the drug development process. Here comes the significance of system biology approaches for inter connecting different scales of drug actions like drug-protein interactions , drug side effects towards side effect prediction for uncharacterized drugs. The emphasis of the study is to extend the systems approaches towards drug discovery for Hepatitis-C by using network analysis. We performed an extensive analysis to retrieve the network of targeted proteins and side effects on the basis of co-occurrence of drugs in protein-binding profiles and side effect profiles. The analysis of 12 drugs with 18 proteins and 14 side effects resulted in the extraction of many correlated sets. This led to a biologically relevant assessment regarding the relationship between drug-targeted proteins and side effects. The identified side effects can be considered as possible phenotypic outcomes by drugs targeting the proteins that appear in the same correlated set. This study is found to be useful in predicting potential side effects of drug candidate compounds based on their protein-binding profiles.

Genome sequencing can play a vital role in health and several other domains such as in nuclear outflow related environmental issues. The power of information derived out of sequencing has been used in the field of health care, evolutionary studies and for better understanding of the biological framework of life. Through the recent advancements in sequencing studies, now the researchers are aiming to use its power in non conventional areas. Here we have discussed on the importance of sequencing the Closterium moniliferum genome which will prove to be a future endeavour in nuclear cleanup and radioactive waste disposal.

Phylogenomics, the use of large-scale data matrices in phylogenetic analyses, has been viewed as the ultimate solution to the problem of resolving difficult nodes in the tree of life. However, it has become clear that analyses of these large genomic datasets can also result in conflicting estimates of phylogeny. Here we use the early divergences in Neoaves, the largest clade of extant birds, as a 'model system' to understand the basis for incongruence among phylogenomic trees. We were motivated by the observation that trees from two recent avian phylogenomic studies exhibit conflicts. Those studies used different strategies: 1) collecting many characters [∼42 mega base pairs (Mbp) of sequence data] from 48 birds, sometimes including only one taxon for each major clade; and 2) collecting fewer characters (∼0.4 Mbp) from 198 birds, selected to subdivide long branches. However, the studies also used different data types: the taxon-poor data matrix comprised 68% non-coding seque...

Phylogenomics has revolutionized the study of evolutionary relationships. However, genome-scale data have not been able to resolve all relationships in the tree of life. This could reflect the poor-fit of the models used to analyze heterogeneous datasets; that heterogeneity is likely to have many explanations. However, it seems reasonable to hypothesize that the different patterns of selection on proteins based on their structures might represent a source of heterogeneity. To test that hypothesis, we developed an efficient pipeline to divide phylogenomic datasets that comprise proteins into subsets based on secondary structure and relative solvent accessibility. We then tested whether amino acids in different structural environments had different signals for the deepest branches in the metazoan tree of life. Sites located in different structural environments did support distinct tree topologies. The most striking difference in phylogenetic signal reflected relative solvent accessibi...

Phylogenomics, the use of large datasets to examine phylogeny, has revolutionized the study of evolutionary relationships. However, genome-scale data have not been able to resolve all relationships in the tree of life; this could reflect, at least in part, the poor-fit of the models used to analyze heterogeneous datasets. Some of the heterogeneity may reflect the different patterns of selection on proteins based on their structures. To test that hypothesis, we developed a pipeline to divide phylogenomic protein datasets into subsets based on secondary structure and relative solvent accessibility. We then tested whether amino acids in different structural environments had distinct signals for the topology of the deepest branches in the metazoan tree. The most striking difference in phylogenetic signal reflected relative solvent accessibility; analyses of exposed sites (on the surface of proteins) yielded a tree that placed ctenophores sister to all other animals whereas sites buried ...

MotivationProtein sequence evolution is a complex process that varies among-sites within proteins and across the tree of life. Comparisons of evolutionary rate matrices for specific taxa (‘clade-specific models’) have the potential to reveal this variation and provide information about the underlying reasons for those changes. To study changes in patterns of protein sequence evolution we estimated and compared clade-specific models in a way that acknowledged variation within proteins due to structure.ResultsClade-specific model fit was able to correctly classify proteins from four specific groups (vertebrates, plants, oomycetes, and yeasts) more than 70% of the time. This was true whether we used mixture models that incorporate relative solvent accessibility or simple models that treat sites as homogeneous. Thus, protein evolution is non-homogeneous over the tree of life. However, a small number of dimensions could explain the differences among models (for mixture models ~50% of the...

Background Previous phylogenetic studies that include the four recognized species of Gallus have resulted in a number of distinct topologies, with little agreement. Several factors could lead to the failure to converge on a consistent topology, including introgression, incomplete lineage sorting, different data types, or insufficient data. Methods We generated three novel whole genome assemblies for Gallus species, which we combined with data from the published genomes of Gallus gallus and Bambusicola thoracicus (a member of the sister genus to Gallus). To determine why previous studies have failed to converge on a single topology, we extracted large numbers of orthologous exons, introns, ultra-conserved elements, and conserved non-exonic elements from the genome assemblies. This provided more than 32 million base pairs of data that we used for concatenated maximum likelihood and multispecies coalescent analyses of Gallus. Results All of our analyses, regardless of data type, yielde...

Despite the long history of using protein sequences to infer the tree of life, the potential for different parts of protein structures to retain historical signal remains unclear. We propose that it might be possible to improve analyses of phylogenomic datasets by incorporating information about protein structure. We test this idea using the position of the root of Metazoa (animals) as a model system. We examined the distribution of “strongly decisive” sites (alignment positions that support a specific tree topology) in a dataset comprising >1500 proteins and almost 100 taxa. The proportion of each class of strongly decisive sites in different structural environments was very sensitive to the model used to analyze the data when a limited number of taxa were used but they were stable when taxa were added. As long as enough taxa were analyzed, sites in all structural environments supported the same topology regardless of whether standard tree searches or decisive sites were used to...