Molecular inhibition of telomerase recruitment using designer peptides: an <i>in silico</i> approach

<div><p>Telomere holds special mechanism for solving end repair problems and maintaining genomic stability. Protection of telomeres 1 (POT1) which belongs to shelterin family is identified as a key protein that recruits telomerase by interacting with telomere repeat binding factors (TRB1-3). Since, deciphering the mechanism through which POT assembles telomerase is of great interest, computational approaches have been undertaken to understand the mechanism in a well- developed model system – <i>Arabidopsis thaliana.</i> As a first step, an untraditional approach was mediated to locate the active site residues on modeled AtPOT1b protein by interaction studies using molecular docking. To keep in trend with the recent developments, peptide construction and validation was promoted as the next step via molecular dynamics simulation studies. Finally, the validated peptides based on propensity score was evaluated for its efficacy as a potent inhibitor for POT and TRB1-3 interactions. The best peptide, namely, (1-2-d) out of 30 designed peptides, was proved to be vital inhibitor by weakening the interacting complexes.</p></div

Identification of lncRNA and weighted gene coexpression network analysis of germinating Rhizopus delemar causing mucormycosis

ABSTRACTRhizopus delemar, an opportunistic fungal pathogen, causes a highly fatal disease, mucormycosis. Spore germination is a crucial mechanism for disease pathogenesis. Thus, exploring the molecular mechanisms of fungal germination would underpin our knowledge of such transformation and, in turn, help control mucormycosis. To gain insight into the developmental process particularly associated with cell wall modification and synthesis, weighted gene co-expression network analysis (WGCNA) was performed including both coding and non-coding transcripts identified in the current study, to find out the module of interest in the germination stages. The module-trait relationship identified a particular module to have a high correlation only at the resting phase and further analysis revealed the module to be enriched for protein phosphorylation, carbohydrate metabolic process, and cellular response to stimulus. Moreover, co-expression network analysis of highly connected nodes revealed cell wall modifying enzymes, especially those involved in mannosylation, chitin-glucan crosslinking, and polygalacturonase activities co-expressing and interacting with the novel lncRNAs among which some of them predicted to be endogenous target mimic (eTM) lncRNAs. Hence, the present study provides an insight into the onset of spore germination and the information on the novel non-coding transcripts with key cell wall–related enzymes as potential targets against mucormycosis