Hydrophobic Groups Stabilize the Hydration Shell of 2′-O-Methylated RNA Duplexes

The simple replacement of 2′-OH by 2′-OMe groups leads, in certain RNA structures, to a significant strengthening of important solute–solvent interactions. Molecular dynamics simulations uncover the complexity of effects associated with the insertion of hydrophobic groups into hydrophilic systems (the arrow indicates a long-lived bridging water molecule located in the shallow groove of a 2′-OMe(GpC) base pair step). Green=skeleton of cytosine, black=skeleton of guanine, red=oxygen atoms of water and of shallow groove carbonyl groups, blue=shallow groove nitrogen atoms, cyan=hydrogen atoms of OMe groups.