Computational Discovery Of The Electronegative Channel In RNA Loop-loop Interactions

Abstract

The most common motifs found in nature and used in bionanotechnology are hairpin loops which consist of a helical part and a loop with unpaired residues. The unpaired residues in these elements can lead to further super-assembly of RNA structures via formation of the loop-loop interactions. These loop-loop interactions regulate biological functions in both prokaryotic and eukaryotic organisms such as gene expression in different viruses and are also actively used in bionanotechnology for self-assembly of RNA building blocks into novel nanostructures. It has been observed that the super-assembly of RNA directly depends on the presence and specific concentration of ions. In order to understand the role of ions in loop-loop formation and stability, we conducted a series of explicit solvent atomistic molecular dynamics simulations of distinct kissing loops elements taken from various organisms. In our simulations we varied the concentration of different ions (such as Na+, K+, Mg2+, and Cl−) from zero to 1M solution and examined known destabilizing mutations. We discovered that in most organisms the loop-loop assembly process depends on the presence of electronegative and hydration channel. The properties of this channel are independent of the concentration and the type of ions. The size of this channel and RNA sequence determines the stability. We also examined the formation of the channel during self-assembly and discovered the critical threshold for the channel formation.