Mg binding (localization) option

Wayne K. Dawson

Setting the Mg binding option to yes causes the program to consider the interaction of Mg in the structure.

For the most part, Mg$^{2+}$ does not bind to the RNA directly because of its large hydration free energy. Mg$^{2+}$ usually exists as a hexa-aquo complex of the form [Mg(H$_2$O)$_6$]$^{2+}$ that is inert to almost all interactions. That is why MgO is also an excellent refractory material (a substance that is very resistant to heat) and is used for firebrick in a refining furnace. MgO can withstand enormous temperatures without damage (up to 2800 K). Considering these observations of MgO, it should not be all that surprising that [Mg(H$_2$O)$_6$]$^{2+}$ is also quite inert.

Typically, [Mg(H$_2$O)$_6$]$^{2+}$ gets trapped in pockets of folded RNA, but never actually binds directly to any specific atoms in the RNA structure. It follows that the observed contribution of [Mg(H$_2$O)$_6$]$^{2+}$ to specific site binding is typically minor. However, on some occasions, there are observable minor effects. One should not expect that the Mg can cause major structural changes in the RNA unless there is a particularly well-defined binding site. Most such sites are not well established at this time, and therefore, most of the so-called ``Mg binding'' interactions used here are also small.

More than mere binding or localization of Mg at specific sites, the primary effect of Mg binding is help stabilize the RNA and cause it to collapse into a globular structure. This effect is better approximated by invoking the ``-flory'' option in the check box. The Flory model can be run as a McKenzie-Moore-Domb-Fisher model or as a JS model.

At present, the nature of Mg (and other divalent cations) is not well known so almost all the values are rough estimates based upon scant affinity data. The effects of solvation should not be ignored because a large cloud of [Mg(H$_2$O)$_6$]$^{2+}$ typically surrounds the RNA in a cloud. This ``cloud'' tends to pack the RNA much tighter than would be characteristic of a denatured sequence, and therefore can introduce curious consequences on the folding. Currently, this kind of modeling is beyond the systematic scope of this program.

It is recommended that you use this function if you think Mg may be influencing the structure. If you see no effect, there almost surely is no such influence. If you observe a profound effect, this would be of some surprise even to the authors here, but it might be interesting.