Polycomb group (PcG) proteins have been observed to maintain the pattern of histone by methylation of the histone tail responsible for the gene expression in various cellular processes, of which enhancer of zeste homolog 2 (EZH2) acts as tumor suppressor. Overexpression of EZH2 results in hyper activation found in a variety of cancer. Point mutation on two important residues were induced and the results were compared between the wild type and mutant EZH2. The mutation of Y641 and A677 present in the active region of the protein alters the interaction of the top ranked compound with the newly modeled binding groove of the SET domain, giving a GLIDE score of −12.26 kcal/mol, better than that of the wild type at −11.664 kcal/mol. In depth analysis were carried out for understanding the underlying molecular mechanism using techniques viz. molecular dynamics, principal component analysis, residue interaction network and free energy landscape analysis, which showed that the mutated residues changed the overall conformation of the system along with the residue-residue interaction network. The insight from this study could be of great relevance while designing new compounds for EZH2 enzyme inhibition and the effect of mutation on the overall binding mechanism of the system.
Olfaction, the sense of smell detects and discriminate odors as well as social cues which
influence our innate responses. The olfactory system in human beings is found to be weak as compared
to other animals; however, it seems to be very precise. It can detect and discriminate millions
of chemical moieties (odorants) even in minuscule quantities. The process initiates with the binding
of odorants to specialized olfactory receptors, encoded by a large family of Olfactory Receptor
(OR) genes belonging to the G-protein-coupled receptor superfamily. Stimulation of ORs converts
the chemical information encoded in the odorants, into respective neuronal action-potentials which
causes depolarization of olfactory sensory neurons. The olfactory bulb relays this signal to different
parts of the brain for processing. Odors are encrypted using a combinatorial approach to detect a
variety of chemicals and encode their unique identity. The discovery of functional OR genes and
proteins provided an important information to decipher the genomic, structural and functional basis
of olfaction. ORs constitute 17 gene families, out of which 4 families were reported to contain more
than hundred members each. The olfactory machinery is not limited to GPCRs; a number of non-
GPCRs is also employed to detect chemosensory stimuli. The article provides detailed information
about such olfaction machinery, structures, transduction mechanism, theories of odor perception,
and challenges in the olfaction research. It covers the structural, functional and computational studies
carried out in the olfaction research in the recent past.
Breast cancer is the most common cancer in women both in the developed and less developed countries, and it imposes a considerable threat to human health. Therefore, in order to develop effective targeted therapies against Breast cancer, a deep understanding of its underlying molecular mechanisms is required. The application of deep transcriptional sequencing has been found to be reported to provide an efficient genomic assay to delve into the insights of the diseases and may prove to be useful in the study of Breast cancer. In this study, ChIP-Seq data for normal samples and Breast cancer were compared, and differential peaks identified, based upon fold enrichment (with P-values obtained via t-tests). The Protein–protein interaction (PPI) network analysis was carried out, following which the highly connected genes were screened and studied, and the most promising ones were selected. Biological pathway involved in the process were then identified. Our findings regarding potential Breast cancer-related genes enhances the understanding of the disease and provides prognostic information in addition to standard tumor prognostic factors for future research.
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