IIIT Hyderabad Publications |
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Structure, Dynamics and Stability of Pure and Chemically Modified Nucleic acids Studied via Molecular Dynamics SimulationsAuthors: Suresh Gorle,U Deva Priyakumar Conference: Indo-German Meeting on Modeling Chemical and Biological (Re)Activity (MCBR3 2013) Location NIPER Mohali Date: 2013-02-26 Report no: IIIT/TR/2013/69 AbstractDue to poor stability and nature of low nuclease resistance of pure nucleic acids, a suitable chemical modification is required which improves several factors such as increased cellular uptake, altered duplex conformation and stability. In general, the modifications at ribose sugar (backbone) of the oligonucleotide attribute special features to the duplexes than other modifications. Some of the common modifications include 2'-O-methyl, 2'-O,4'-C-methylene-β-D-ribofuranosyl (LNA) and phosphoroamidate. The modified oligonucleotides have also been shown to be potential antisense agents. Molecular dynamics (MD) simulations are valuable tools to study nucleic acid dynamics, conformational preferences, stabilities etc. Here, we have employed different simulation techniques such as traditional MD, replica exchange MD to understand the properties of modified duplexes and also the origin for the effect of chemical modification. The simulations revealed several important aspects related to duplex stability and relation with their base content. The factors responsible for the stability/unstability of modified duplexes with different sequences are also examined. Our results also suggest that the differential changes observed in nucleic acids depends on the position, nature of the modified site. This study also provides a molecular level picture of structural changes arising due to different types of modifications which is important in designing antisense oligonucleotides. Full paper: pdf Centre for Computational Natural Sciences and Bioinformatics |
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