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Theoretical analysis of antisense duplexes: determinants of the RNase H susceptibility

Posted June 8th, 2010 by pschmidtke
TitleTheoretical analysis of antisense duplexes: determinants of the RNase H susceptibility
Publication TypeJournal Article
Year of Publication2008
AuthorsNoy, A, Luque FJ, Orozco M
JournalJournal of the American Chemical Society
Volume130
Issue11
Pagination3486 - 3496
Date Published2008/03/19/
KeywordsAntisense/chemistry; RNA/chemistry; Ribonuclease H/chemistry, Chemical; Nucleic Acid Conformation; Nucleic Acid Heteroduplexes/chemistry; Oligoribonucleotides, Computer Simulation; DNA/chemistry; Models
AbstractThe structure and dynamic properties of different antisense related duplexes (DNA x RNA, 2'O-Me-DNA x RNA, 2'F-ANA x RNA, C5(Y)-propynyl-DNA x RNA, ANA x RNA, and control duplexes DNA x DNA and RNA x RNA) have been determined by means of long molecular dynamics simulations (covering more than 0.5 micros of fully solvated unrestrained MD simulation). The massive analysis presented here allows us to determine the subtle differences between the different duplexes, which in all cases pertain to the same structural family. This analysis provides information on the molecular determinants that allow RNase H to recognize and degrade some of these duplexes, whereas others with apparently similar conformations are not affected. Subtle structural and deformability features define the key properties used by RNase H to discriminate between duplexes.