Rules governing the orientation of the 2'-hydroxyl group in RNA

Molecular dynamics simulations reveal that, in C-3'-endo sugar puckers, only three orientations are accessible to the 2'-hydroxyl groups distinctive of RNA molecules: towards (i) the O-3', (ii) the O-4' of the same sugar, and (iii) the shallow groove base atoms. Ln the rarer C-2-endo sugar puckers, orientations towards the O3' atom of the same sugar are strongly favoured. Surprisingly, in helical regions, the frequently suggested intrastrand O-2'-H(n)...O-4'(n + 1) interaction is not found. This observation led to the detection of an axial C-H...O interaction between the C-2'-H-2'(n) group and the O-4'(n + 1) atom contributing to the stabilization of RNA helical regions. Subsequent analysis of crystallographic structures of both RNA and A-DNA helices fully supports this finding. Specific hydration patterns are also thought to play a significant role in the stabilization of RNA structures. In the shallow groove of RNA, known as a favourable RNA or protein-binding region, three well-defined hydration sites are located around the O-2' atom. These hydration sites, occupied by water molecules exchanging with the bulk, constitute, after dehydration, anchor points for specific interactions between RNA and nucleic acids, proteins or drugs. Therefore, the fact that the 2'-hydroxyl group is not monopolised by axial stabilization, together with its water-like behaviour, facilitates complex formation involving RNA helical regions. (C) 1997 Academic Press Limited.