Multivalent ion-mediated nucleic acid helix-helix interactions: RNA versus DNA

Abstract

Ion-mediated interaction is critical to the structure and stability of nucleic acids. Recent experiments suggest that the multivalent ion-induced aggregation of double-stranded (ds) RNAs and DNAs may strongly depend on the topological nature of helices, while there is still lack of an understanding on the relevant ion-mediated interactions at atomistic level. In this work, we have directly calculated the potentials of mean force (PMF) between two dsRNAs and between two dsDNAs in Co(NH3)6 (3+) (Co-Hex) solutions by the atomistic molecular dynamics simulations. Our calculations show that at low [Co-Hex], the PMFs between B-DNAs and between A-RNAs are both (strongly) repulsive. However, at high [Co-Hex], the PMF between B-DNAs is strongly attractive, while those between A-RNAs and between A-DNAs are still (weakly) repulsive. The microscopic analyses show that for A-form helices, Co-Hex would become 'internal binding' into the deep major groove and consequently cannot form the evident ion-bridge between adjacent helices, while for B-form helices without deep grooves, Co-Hex would exhibit 'external binding' to strongly bridge adjacent helices. In addition, our further calculations show that, the PMF between A-RNAs could become strongly attractive either at very high [Co-Hex] or when the bottom of deep major groove is fixed with a layer of water.

Figure 1.

An illustration for two parallel 16-bp A-RNAs (A), B-DNAs (B) and A-DNAs (C). The spring with a spring constant k which connects the centers of mass of two helices has been used to calculate the potential of mean force between two double-stranded RNAs and DNAs (53,54,73).

Figure 2.

(A) The potentials of mean force between two 16-bp B-DNAs in 0.5 mM and 5 mM Co-Hex solutions. (B) The Co-Hex ion distributions around the B-DNA corresponding to panel a. (C) The Co-Hex ion distributions around B-DNA in (or over) major groove and minor groove according to panels a and b. (D) The potentials of mean force between two 16-bp A-RNAs in 0.5 mM, 5 mM and 50 mM Co-Hex solutions. (E) The Co-Hex distributions around the A-RNA corresponding to panel d. (F) The Co-Hex distributions around A-RNA in (or over) major groove and minor groove corresponding to panels d and e. Note that the buffers always contain 100 mM NaCl.

Figure 3.

(A and B) The illustrations for the region of high Co-Hex ion charge density (larger than 0.02 e/ų) around two 16-bp B-DNAs in 0.5 mM (a) and 5 mM (b) Co-Hex solutions; (C) The illustration for the region of the high Co-Hex ion charge density (larger than 0.02 e/ų) around two 16-bp A-DNAs in 5 mM Co-Hex solutions. (D–F) The illustrations for the region of high Co-Hex charge density (larger than 0.02 e/ų) around two 16-bp A-RNAs in 0.5 mM (d), 5 mM (e) and 50 mM (f) Co-Hex solutions. Note that the buffers always contain 100 mM NaCl.

Figure 4.

(A) The potentials of mean force between two 16-bp nucleic acid (B-DNA, A-RNA, and A-DNA) helices in 5 mM Co-Hex ion solution; (B) The Co-Hex distribution around the nucleic acid helices corresponding to panel a; (C) The Co-Hex distribution around the nucleic acid helices in (or over) major groove and minor groove corresponding to panels a and b. Note that the buffers always contain 100 mM NaCl.

Figure 5.

The illustrations for the spatially modified A-RNA (A-RNA’ and A-RNA") and the region of the high Co-Hex charge density (larger than 0.02 e/ų) in 5 mM Co-Hex solution around two 16-bp A-RNA's and around two 16-bp A-RNA's. The A-RNA’ denotes the A-RNA with the bottom of the central 1/3 major groove fixed with a layer of water, whereas the A-RNA" denotes the A-RNA with the bottom of the entire major groove fixed with a layer of water. The red-gray chains in deep major grooves illustrate the fixed water molecules. Note that the buffers always contain 100 mM NaCl.

Figure 6.

(A) The potentials of mean force between two 16-bp A-RNAs, between two 16-bp A-RNA's, and between 16-bp A-RNA’'s in 5 mM Co-Hex ion solution; (B) The Co-Hex distributions around the A-RNA, A-RNA’, and A-RNA’’ corresponding to panels a and b; (C) The Co-Hex distributions around the A-RNA, A-RNA’, and A-RNA’’ in (or over) major groove and minor groove corresponding to panels a and b. The A-RNA’ denotes the A-RNA with the bottom of the central 1/3 major groove fixed with a layer of water, whereas the A-RNA" denotes the A-RNA with the bottom of the entire major groove fixed with a layer of water. Note that the buffers always contain 100 mM NaCl.