Molecular Dynamics Simulations Highlight the Structural Differences among DNA:DNA, RNA:RNA, and DNA:RNA Hybrid Duplexes

Abstract

Nanosecond length simulations applying the particle mesh Ewald method within AMBER 4.1 on canonical A-form and B-form geometries of d[CCAACGTTGG]2, r[CCAACGUUGG]2, and d[CCAACGTTGG]−r[CCAACGUUGG] duplexes in aqueous solution are reported. DNA duplexes only adopt a stable B-DNA geometry, in contrast to RNA duplexes which adopt both a stable A-RNA and “B-RNA” geometry. The observation of a stable “B-RNA” structure is somewhat surprising and suggests significant kinetic barriers to structural conversion in RNA structures on a nanosecond time scale. The “B-RNA” can be converted to A-RNA by forcing a concerted flip in the sugar puckers from C2‘-endo to C3‘-endo. The A-RNA structure displays features similar to A-form crystal structures, specifically interstrand purine stacking at the central pyrimidine−purine step is observed. When started in a canonical A-form geometry, DNA:RNA hybrid duplexes converge to a structure that is characteristic of experimental solution structures; specifically, a minor groove widt...