Modelling ion binding to AA platform motifs in RNA: a continuum solvent study including conformational adaptation

Binding of monovalent and divalent cations to two adenine-adenine platform structures from the Tetrahymena group I intron ribozyme has been studied us ing continuum solvent models based on the generalised Born and the finite-d ifference Poisson-Boltzmann approaches. The adenine-adenine platform RNA mo tif forms an experimentally characterised monovalent ion binding site impor tant for ribozyme folding and function. Qualitative agreement between calcu lated and experimental ion placements and binding selectivity was obtained. The inclusion of solvation effects turned out to be important to obtain lo w energy structures and ion binding placements in agreement with the experi ment. The calculations indicate that differences in solvation of the isolat ed ions contribute to the calculated ion binding preference. However, Coulo mb attraction and van der Waals interactions due to ion size differences an d RNA conformational adaptation also influence the calculated ion binding a ffinity. The calculated alkali ion binding selectivity for both platforms f ollowed the order K+ > Na+ > Rb+ > Cs+ > Li+ (Eisenman series VI) in the ca se of allowing RNA conformational relaxation during docking. With rigid RNA an Eisenman series V was obtained (K+ > Rb+ > Na+ > Cs+ > Li+). Systematic energy minimisation docking simulations starting from several hundred init ial placements of potassium ions on the surface of platform containing RNA fragments identified a coordination geometry in agreement with the experime nt as the lowest energy binding site. The approach could be helpful to iden tify putative ion binding sites in nucleic acid structures determined at lo w resolution or with experimental methods that do not allow identification of ion binding sites.