  The highly charged RNA molecules, with each phosphate carrying a single
negative charge, cannot fold into well-defined architectures with tertiary
interactions, in the absence of ions. For ribozymes, divalent cations are known
to be more efficient than monovalent ions in driving them to a compact state
although Mg$^{2+}$ ions are needed for catalytic activities. Therefore, how
ions interact with RNA is relevant in understanding RNA folding. It is often
thought that most of the ions are territorially and non-specifically bound to
the RNA, as predicted by the counterion condensation (CIC) theory. Here, we
show using simulations of ${\it Azoarcus}$ ribozyme, based on an accurate
coarse-grained Three Site Interaction (TIS) model, with explicit divalent and
monovalent cations, that ion condensation is highly specific and depends on the
nucleotide position. The regions with high coordination between the phosphate
groups and the divalent cations are discernible even at very low Mg$^{2+}$
concentrations when the ribozyme does not form tertiary interactions.
Surprisingly, these regions also contain the secondary structural elements that
nucleate subsequently in the self-assembly of RNA, implying that ion
condensation is determined by the architecture of the folded state. These
results are in sharp contrast to interactions of ions (monovalent and divalent)
with rigid charged rods in which ion condensation is uniform and position
independent. The differences are explained in terms of the dramatic
non-monotonic shape fluctuations in the ribozyme as it folds with increasing
Mg$^{2+}$ or Ca$^{2+}$ concentration.
