One of the largest challenges facing structural biologists is to predict the structure of complex molecules in aqueous solution. In this article we show for the first time that Locally Enhanced Sampling can be used in conjunction with the recently implemented Particle-Mesh-Ewald method to address this challenge. We present results from studies of a small RNA tetraloop system (5＇-r[GGACUUCGGUCC]) where this combined protocol has allowed our simulations to rapidly find the experimental structure starting from an alternate location in phase space.