From RNA sequence to its three-dimensional structure: geometrical structure, stability and dynamics of selected...

In this computational study, we explore the folding of a particular sequence using various computational tools to produce two-dimensional structures, which are then transformed into three-dimensional structures. We then study the geometry, energetics and dynamics of these structures using full electron quantum-chemical and classical molecular dynamics calculations. Our study focuses on the SARS-CoV-2 RNA fragment GGaGGaGGuguugcaGG and its various structures, including a G-quadruplex and five different hairpins. We examine the impact of two types of counterions (K⁺ and Na⁺) and flanking nucleotides on their geometrical characteristics, relative stability and dynamic properties. Our results show that the G-quadruplex structure is the most stable among the constructed hairpins. We confirm its topological stability through molecular dynamics simulations. Furthermore, we observe that the nucleotide loop consisting of seven nucleotides is the most flexible part of the RNA fragment. Additionally, we find that RNA networks of intermolecular hydrogen bonds are highly sensitive to the surrounding environment. Our findings reveal the loss of 79 old hydrogen bonds and the formation of 91 new ones in the case when the G-quadruplex containing flanking nucleotides is additionally stabilized by Na⁺ counterions.