Both WT and A29C RNAs were initially built in an ideal A-form helical configuration and served as the starting conformation in every simulation of REMD. The RNA was solvated in an 80-Å cubic box of pre-equilibrated TIP3P water (approximately 50 000 atoms). Twelve pairs of sodium chloride with an additional 11 sodium ions were added to the box, corresponding to the experimental ionic concentration of 40 mM.