System preparation and Molecular Dynamics (MD) simulations. Simulations were carried out with the AMBER 18 simulation package using the PARM99 force field with revised χ and α/γ 37 torsional parameters. The NAB 38 module of AMBER 18 was utilized to build the initial structures of r(5′-UCUGGGGCCAGA-3′)2, r(5′-UCUGGCCCCAGA-3′)2 and r(5′-UCUCCCCGGAGA-3′)2 in A-form RNA orientations, where underlined regions display the 2×2 internal loops. Each system was first neutralized with Na + ions , which then was solvated with TIP3P water molecules in a truncated octahedral box with periodic boundary conditions extending to 10 Å using the LEAP module of AMBER 18. The structures were minimized with the sander module each in two steps. Positional restraints on RNA heavy atoms with restraint weights of 10 kcal mol -1 Å -2 were applied in the first step of minimization with 2500 steps of steepest-descent algorithm followed by 2500 steps of conjugate-gradient algorithm. Second round of minimization was performed without restraints with 2500 steps of steepest-descent algorithm followed by 2500 steps of conjugate-gradient algorithm (Table ). Minimization was followed by an equilibration protocol first in constant volume dynamics, where positional restraints were imposed on the RNA heavy atoms with restraint weights of 10 kcal mol -1 Å -2 while temperature was gradually increased from 0 K to 300 K within several nanoseconds using the Langevin thermostat (Table ). A second round of equilibration was performed at constant pressure , where temperature and pressure coupling were set to 300 K and 1.0 ps -1 , respectively, while constraints on the solute were gradually removed (Table ). After minimization and equilibration, MD simulation with a 2 ps time step was performed on each system using NPT dynamics with isotropic positional scaling. The reference pressure was set to 1 atm with a pressure relaxation time of 2 ps. SHAKE was turned on for constraining bonds involving hydrogen atoms. An atom-based long-range cutoff of 10.0 Å was used in the production runs. The reference temperature was set to 300 K. PME was used to handle the electrostatics and the Langevin thermostat was applied with a coupling constant γ = 1.0 ps -1 . Simulations were performed using the pmemd.cuda implementation of AMBER18.