However, we have observed the following discrepancies in the free energy estimates based on our micro-second time scale simulations. i) The free energy values and sampling are dependent on the choice of collective variables for biasing. ii) The system tries to exist in trapped false minima states, fails to provide converged free energy surfaces (Figs S6, S7 of SI). The main reason for this is poor choice of collective variables in the complex multidimensional landscape. This leads to improperly oversampling of the trapped state resulting in a high barrier for transitions to other states. The previous studies on similar RNA motifs also encountered similar issues especially related to a lack of convergence with respect to the choice of collective variables, technique, and force field parameters. The understanding from our unreported well-tempered metadynamics simulations and the need for using multiple collective variables for chasing the multi-dimensional free energy landscape directed us to use a combination of two enhanced sampling techniques, umbrella sampling and parallel bias metadynamics.