In silico modeling of ligand molecule for non structural 3 (NS3) protein target of flaviviruses.

UNLABELLED: Flaviviruses are small, enveloped RNA viruses which cause a variety of diseases into animals and man. Despite the existence of licensed vaccines, yellow fever, Japanese encephalitis and tick-borne encephalitis also claim many thousands of victims each year across their vast endemic areas. A number of studies have already revealed that the non-structural NS3 serine protease is required for the maturation of the viral polyprotein and thus is a promising target for the development of antiviral inhibitors. Hence, the 3D structure of NS3 protein was modeled using homology modeling by MODELLER 9v7. Validation of the constructed NS3 protein models were done by PROCHECK, VERYFY3D and through ProSA calculations. Ligands for the catalytic triad (H51, D75, and S135) were designed using LIGBUILDER. The NS3 protein's catalytic triad was explored to find out the interactions pattern for inhibitor binding using molecular docking methodology using AUTODOCK Vina. The interactions of complex NS3protein-ligand conformations, including hydrogen bonds and the bond lengths were analyzed using Accelrys DS Visualizer software. Hence, from this observation, the novel molecule designed was observed to be the best ligand against the NS3 protein of flavivirus. This molecule may prove to be a potential identity in modulating disease manifestation for all the selected flavivirus members. ABBREVIATIONS: NCBI - National Centre for Biotechnological Information, BLAST - Basic Local Alignment Search Tool, DOPE - Discrete optimized protein energy, GROMOS96 - GROningen MOlecular Simulation package, SAVS - Structure Analysis and Validation Server.

Annotation of hypothetical proteins orthologous in Pongo abelii and Sus scrofa.

UNLABELLED: A hypothetical protein is predicted to be expressed from an open reading frame without known experimental evidence of translation. They constitute a substantial fraction of proteomes. Domain extraction from these hypothetical sequences helps to search for protein coding genes for protein structural and functional annotation. We describe the analysis of prediction data in a sequence dataset of hypothetical protein orthologs of Pongo abelii (orangutan) and Sus scrofa (pig). It should be noted that these orangutan-pig orthologs are also non-homologous to human proteins. These predicted data find application in the genome wide annotation of proteins in poorly understood genomes. ABBREVIATIONS: PDB - Protein Data Bank, DEG - Database of Essential Genes, CDD - Conserved Domain Database, IUCN - International Union for Conservation of Nature.