Types and concentrations of metal ions affect local structure and dynamics of RNA

The roles that metal ions play in the structure and dynamics of RNA molecules are long-standing problems that have been studied extensively but are still not well understood. Here we show that metal ions have distributions around RNA molecules that strongly depend on the types and concentrations of the metal ions and also the electrostatic surface of the molecule. In particular, the ion distributions may not balance all the local electronegativity of the molecule. These ion distributions do not only greatly affect local structures but also lead to different local dynamics of RNA. We studied the effects of different ion solutions on the structure and dynamics of RNA by taking the $\mathrm{pre}{\mathrm{Q}}_1$ riboswitch aptamer domain as an illustrative example and using molecular dynamics simulations. Since the local structures and dynamics of RNAs are important to their functions, our results also indicate that the selection of proper ion conditions is necessary to model them correctly, in contrast to the use of diverse ion solutions in current molecular dynamics simulations.

Figure 1

Structures and electrostatic surface of the bound $\mathrm{pre}{\mathrm{Q}}_1$ riboswitch aptamer domain (PDB ID: 2L1V). (a) Secondary and (b) tertiary structures; (c) and (d) different views of the electrostatic surface. In (a) and (b) different components (P1, P2, L1, L2, and L3) are coded in color and the ligand $\mathrm{pre}{\mathrm{Q}}_1$ is represented by a stick model. In (c) and (d) the electrostatic potential increases from red (dark) to blue (light).

Figure 2

The distribution of metal ions in different ion conditions. The distribution of sodium ions, potassium ions, and magnesium ions are colored in blue, red, and green, respectively. The dark color in the figure shows the positions where the ions remain for a long time. (a)–(c) are solutions with neutralizing $\mathrm{N}{\mathrm{a}}^{+},{\mathrm{K}}^{+}$, and $\mathrm{M}{\mathrm{g}}^{2+}$ ions, respectively; (d)–(f) are solutions with neutralizing $\mathrm{N}{\mathrm{a}}^{+}$ ions and extra $0.3M$ NaCl, $0.3M$ KCl, and $0.15M\mathrm{MgC}{\mathrm{l}}_2$, respectively; (g)–(i) are solutions with neutralizing ${\mathrm{K}}^{+}$ ions and extra $0.3M$ NaCl, $0.3M$ KCl, and $0.15M\mathrm{MgC}{\mathrm{l}}_2$, respectively.

Figure 3

The distribution of $\mathrm{M}{\mathrm{g}}^{2+}$ ions around the $\mathrm{pre}{\mathrm{Q}}_1$ riboswitch aptamer domain in a solution with only neutralizing $\mathrm{M}{\mathrm{g}}^{2+}$ ions and their interactions with the backbone phosphate groups. (a) The distribution of $\mathrm{M}{\mathrm{g}}^{2+}$ ions around the $\mathrm{pre}{\mathrm{Q}}_1$ riboswitch aptamer domain; (b) one $\mathrm{M}{\mathrm{g}}^{2+}$ ion interacts with two phosphate groups; (c) two $\mathrm{M}{\mathrm{g}}^{2+}$ ions interact with one phosphate group. $\mathrm{M}{\mathrm{g}}^{2+}$ ions are represented by the green balls, the entire molecule is in blue, and the oxygen and phosphate atoms of the phosphate groups are in red and cyan, respectively.

Figure 4

Boxplot of RMSD of different regions in MD simulations. (a)–(c) are solutions with neutralizing $\mathrm{N}{\mathrm{a}}^{+},{\mathrm{K}}^{+}$, and $\mathrm{M}{\mathrm{g}}^{2+}$ ions, respectively; (d)–(f) are solutions with neutralizing $\mathrm{N}{\mathrm{a}}^{+}$ ions and extra $0.3M$ NaCl, $0.3M$ KCl. and $0.15M\mathrm{MgC}{\mathrm{l}}_2$, respectively; (g)–(i) are solutions with neutralizing ${\mathrm{K}}^{+}$ ions and extra $0.3M$ NaCl, $0.3M$ KCl, and $0.15M\mathrm{MgC}{\mathrm{l}}_2$, respectively; (j) is the solution without any ions. The lower and upper horizontal line is the minimum and maximum value, respectively. The lower and upper edge of the box is the first and third quantile, respectively. The middle line in the box is the median. “W” denotes the entire molecule.

Figure 5

Hydrogen bond occupancies in three trajectories of molecular dynamics (MD) simulations without any added ions. The blue color represents the unbroken base pair; the purple and red color denotes a G-C base pair with one or two broken hydrogen bonds (H-bond), respectively; the cyan color stands for an A-U base pair with one broken H bond; the white color represents the entirely broken base pairs.