Molecular-dynamics studies of single-stranded hexitol, altritol, mannitol, and ribose nucleic acids (HNA, MNA, ANA, and RNA, resp.) and of the stability of HNA·RNA, ANA·RNA, and MNA·RNA duplexes
Froeyen M., Wroblowski B., Esnouf R., De Winter H., Allart B., Lescrinier E., Herdewijn P.
The influence of the orientation of a 3'-OH group on the conformation and stability of hexitol oligonucleotides in complexes with RNA and as single strands in aqueous solution was investigated by molecular-dynamics (MD) simulations with AMBER 4.1. The particle mesh Ewald (PME) method was used for the treatment of long-range electrostatic interactions. An equatorial orientation of the 3'-OH group in the single-stranded D-mannitol nucleic acid (MNA) m(GCGTAGCG) and in the complex with the RNA r(CGCAUCGC) has an unfavorable influence on the helical stability. Frequent H-bonds between the 3'-OH group and the O-C(6') of the phosphate backbone of the following nucleotide explain the distorted conformation of the MNA·RNA complex as well as that of the single MNA strand. This is consistent with experimental results that show lowered hybridization potentials for MNA·RNA complexes. An axial orientation of the 3'-OH group in the D-altritol nucleic acid (ANA) a(GCGTAGCG) leads to a stable complex with the complementary RNA r(CGCAUCGC), as well as to a more highly preorganized single-stranded ANA chain. The averaged conformation of the ANA·RNA complex is similar to that of A-RNA, with only minor changes in groove width, helical curvature, and H-bonding pattern. The relative stabilities of ANA·RNA vs. HNA·RNA (HNA = D-hexitol nucleic acid without 3'-OH group) can be explained by differences in restricted movements, H-bonds, and solvation effects.