Molecular dynamics simulations of RNA molecules consisting of an antisense oligonucleotide forming a complex with a target strand thereby creating an internal bulge-loop with 3, 4, or 5 nucleotides have been performed with and without O2? methylation of the antisense strand. The methylation influcences minor groove hydration, in particular near guanines but also around the methylated O2?, and it also reduces the flexibility of both RNA strands. A G·U wobble pair adjacent to the bulge-loop is also found to increase the flexibility of the bulge nucleotides, compared to the situation with a standard Watson-Crick G-C base-pair in the same position.

Key words: Molecular dynamics; Simulation.