http://dspace.bits-pilani.ac.in:8080/jspui/handle/123456789/1922 2026-04-21T16:47:04Z http://dspace.bits-pilani.ac.in:8080/jspui/handle/123456789/20535 The multifaceted role of lncRNA MEG3 in kidney disease: a focus on mechanisms, therapeutic and diagnostic potential Majumder, Syamantak; Gaikwad, Anil Bhanudas Kidney disease represents a global health challenge, affecting millions of people and contributing to significant morbidity and mortality. Long noncoding RNAs are potentially emerging as regulators in cellular processes and are involved in pathophysiological alterations in kidney disease. Among these, MEG3 has gained attention for its diverse regulatory roles in fibrosis, apoptosis and inflammation. MEG3 dysregulation has been implicated in conditions like chronic kidney disease, acute kidney injury, diabetic kidney disease and renal cell carcinoma. However, its involvement in endoplasmic reticulum (ER) stress and autophagy, crosstalk in kidney disease, is poorly understood. Hence, this review aims to highlight the role of MEG3 as a therapeutic and diagnostic viewpoint in kidney disease and its regulatory mechanism in ER stress and autophagy. 2025-09-01T00:00:00Z http://dspace.bits-pilani.ac.in:8080/jspui/handle/123456789/20534 Molecular mechanism of the enhanced viral fitness contributed by secondary mutations in the hemagglutinin protein of oseltamivir resistant H1N1 influenza viruses: Modeling studies of antibody and receptor binding Basu, Sushmita The envelope protein hemagglutinin (HA) of influenza viruses is primarily associated with host antibody and receptor interactions. The HA protein is known to maintain a functional balance with neuraminidase (NA), the other major envelope protein. Prior to 2007–2008, human seasonal H1N1 viruses possessing the NA H274Y mutation, which confers oseltamivir resistance, generally had low growth capability. Subsequently, secondary mutations that compensate for the deleterious effect of the NA H274Y mutation have been identified. The molecular mechanism of how the defect could be counteracted by these secondary mutations is not fully understood. We studied here the effect of three such mutations (T86K, K144E and R192K) in the HA protein, which are located at either the HA receptor binding site or in the H1N1 antigenic sites. Molecular docking and dynamics studies showed that, of the three mutations, the R192K mutation could have mediated neutralizing antibody escape and decreased receptor binding affinity, either or both of which may have contributed to increased viral fitness. The study suggests the molecular basis of enhanced viral fitness induced by secondary mutations in the evolution of oseltamivir-resistant influenza strains. 2015-02-01T00:00:00Z http://dspace.bits-pilani.ac.in:8080/jspui/handle/123456789/20533 A structural perspective of RNA recognition by intrinsically disordered proteins Basu, Sushmita Protein-RNA recognition is essential for gene expression and its regulation, which is indispensable for the survival of the living organism at one hand, on the other hand, misregulation of this recognition may lead to their extinction. Polymorphic conformation of both the interacting partners is a characteristic feature of such molecular recognition that promotes the assembly. Many RNA binding proteins (RBP) or regions in them are found to be intrinsically disordered, and this property helps them to play a central role in the regulatory processes. Sequence composition and the length of the flexible linkers between RNA binding domains in RBPs are crucial in making significant contacts with its partner RNA. Polymorphic conformations of RBPs can provide thermodynamic advantage to its binding partner while acting as a chaperone. Prolonged extensions of the disordered regions in RBPs also contribute to the stability of the large cellular machines including ribosome and viral assemblies. The involvement of these disordered regions in most of the significant cellular processes makes RBPs highly associated with various human diseases that arise due to their misregulation. 2016-05-01T00:00:00Z http://dspace.bits-pilani.ac.in:8080/jspui/handle/123456789/20532 Effect of neighbouring residues in conformational plasticity of intrinsically disordered proteins Basu, Sushmita Effect of neighbouring residues in conformational plasticity of intrinsically disordered regions. The concept of unstructured proteins has opened new avenues in the field of structural biology. Intrinsically disordered proteins (IDPs) are the new class of proteins which have been found to be a major player in many significant cellular functions. IDPs have been characterised by its physicochemical properties as well as its molecular interaction behaviour. Detailed study of IDPs can lead to a better understanding of protein folding and its functioning. To understand the source of disorderedness in the disordered regions (IDRs) in IDPs, we studied how the sequence environment of a disordered region correlates to its randomness. Here, we analysed the physicochemical and structural features like amino acid propensities, net charge, hydropathy index, secondary structure propensity, relative surface accessibility, interaction density and H-bonds to characterise the neighbours of the IDRs. Five residues, each towards N and C terminal of the disordered region are considered as the neighbours of IDRs. These neighbouring residues are found to be enriched in disorder promoting amino acids and have higher propensity to form loops than other secondary structures. Solvent accessibility of neighbouring residues also showed increasing trend as we move towards the IDRs. The variation of other parameters along with the above observation indicates that the neighbouring residues of IDRs induce a degree of flexibility to the adjoining IDRs. Based on our findings, we are designing an algorithm using random forest, which shall predict the disordered region based on its neighbouring sequences. The information on IDRs and its neighbours can be useful for proteins to be expressed or characterised for the first time. It can also provide a lead in understanding the molecular mechanism behind the polymorphic interactions that are involved with IDPs. 2018-02-01T00:00:00Z