IIIT Hyderabad Publications |
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Molecular Insights into the Switching Mechanism of add A-RiboswitchAuthors: Abhijit Mitra Conference: International Conference on Physics Biology Interface (ICPBI2009 2009) Date: 2009-12-13 Report no: IIIT/TR/2009/202 AbstractRiboswitches are ligand dependent regulatory elements, found in mRNA transcripts, which are composed of two distinct, yet mutually interacting domains: a ‘ligand-binding’ or aptamer domain and an expression platform involved in gene regulation. Conformational changes due to ligand binding, controls downstream gene expressions. Purine riboswitches have been widely investigated for their remarkable ligand specificity and variation in functional mechanism, despite their sequence similarities. Yet, a complete molecular level understanding of the mechanism of ligand binding, ligand discrimination and switching is still limited because the characterization of the ligand-free OPEN state is limited primarily to results derived from chemical probing, NMR, fluorescence, single labeled FRET and single molecule force spectroscopy experiments. We have carried out ab initio quantum chemical studies on the binding pocket1 and studied explicit-solvent molecular dynamics simulations of the aptamer domain of the adenine riboswitch both in the adenine-bound (CLOSED) and the adenine-free (OPEN) state.2 Dynamic cross correlation, root mean square fluctuation and backbone torsion angle analyses of the trajectories and analysis of the average OPEN and CLOSED state structures, reveal alternative hydrogen bonding schemes leading to the switch and provides molecular level explanations for existing experimental data related to the ligand binding and switching process. Full paper: pdf Centre for Computational Natural Sciences and Bioinformatics |
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