IIIT Hyderabad Publications |
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Quantum Mechanical Investigation of the Nature of RNA base-Urea Stacking InteractionsAuthor: NITISH Alodia Date: 2019-04-05 Report no: IIIT/TH/2019/27 Advisor:Deva U Priyakumar AbstractUrea assisted denaturation of protein and RNA has been shown to be a valuable tool for studying the stabilities and the folding phenomena of these biomolecules. It has been shown that stacking interactions between nucleobases and urea are one of the driving forces of denaturation. In this study, the ability of urea to form unconventional stacking interactions with RNA bases is investigated by performing high level quantum calculations (RI-MP2/aug-cc-pVDZ level) on few thousands of model systems. Four systems were considered based on the RNA nucleobases (GUA, ADE, CYT, and URA) for the investigation. For each system, a set of models were designed to study the role of hetero-atoms/groups of the nucleobases on stacking interactions with urea moiety with respect to every possible pair. Furthermore, for each model, several plane parallel complexes were generated with urea on top of aromatic systems to exhaustively study all possible factors for urea-nucleobases stacking interactions. Energy decomposition analysis (EDA) and natural bond orbital (NBO) analysis were performed on stacked complexes. AIM analysis was done for the most stable system of each model for all systems to gain better insights on non-covalent stacking interactions. Dispersion component was found to be heavily stabilizing, while the EHF was found to be repulsive for all the four systems indicating lack of hydrogen bonding (HB) type interactions and presence of dispersion type interactions. Interactions of most stable complex for each nucleobase with Urea moeities were also studied to identify the importance of each part of Urea in these stacking interactions. Amide and Carbonyl group of urea molecule was found to play a major role in stacking interactions. We demonstrate that along with functional groups present on the nucleobases, the orientation of urea molecules plays a vital role in stabilizing the urea-nucleobase non-covalent interactions. The proposed study quantifies and provides a comprehensive theoretical description of urea nucleobase unconventional stacking interactions which helps to unravel urea driven RNA unfolding mechanism. Full thesis: pdf Centre for Computational Natural Sciences and Bioinformatics |
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