Importance of Anion−π Interactions in RNA GAAA and GGAG Tetraloops: A Combined MD and QM Study

[Image: see text] In this study, we demonstrate that anion−π interactions (an attractive noncovalent force between electron deficient π-systems and anions) are involved in the stabilization of GAAA and GGAG RNA tetraloops. Using the single recognition particle (SRP)–RNA complexes as a case of study, we combined molecular dynamics (MD) and quantum mechanics (QM) calculations to shed light on the structural influence of phosphate–G anion−π interactions and hydrogen bonds (HBs) involving K(+)/Mg(2+) water clusters. In addition, the RNA assemblies herein were further characterized by means of the “atoms in molecules” (AIM) and noncovalent interactions plot (NCIplot) methodologies. We believe the results derived from this study might be important in the fields of chemical biology (RNA folding and engineering) and supramolecular chemistry (anion−π interactions) as well as to further expand the current knowledge regarding RNA structural motifs.