At first, we used the radius of gyration of RNA and native hydrogen bonds in the stem region of the RNA motif for welltempered metadynamics simulation (section 1 and Figs. in the Supporting information (SI)). However, we identified that the given choice of collective variables failed to distinguish similar states specifically in the loop region, which consists of the sugar-backbone hydrogen bonds (Fig. of SI). Reweighting the free energy surface with respect to ermsd showed encouraging results (Fig. of SI). We then incorporated, modified, and used various combinations of CVs (Figs. S5) for welltempered metadynamics limited to a maximum of two per combination to tackle the problems faced in defining the initially constructed reaction coordinate setup. Details of these simulations are provided in the SI.