RNAs can act as potential drug targets in different diseases as their dysregulated expression or misfolding can alter various cellular processes. Non-coding RNAs account for ∼70% of the human genome and can have complex tertiary structures that present a great opportunity to be targeted by small molecules. Until recently, the majority of structure-based drug discovery efforts have been focused on targeting proteins; however, with greater understanding of RNA structures and functions, it is now within our reach to transfer and apply computer-aided drug design methods from protein targets to RNA targets. Site Identification by Ligand Competitive Saturation (SILCS) is a unique computational approach that provides a comprehensive 3D characterization of a target macromolecule in the form of functional group affinity maps, termed grid free energy (GFE) FragMaps obtained through enhanced sampling simulations of the macromolecule in an aqueous solution containing a range of chemical probes. The GFE FragMaps can be used to dock small molecule ligands using SILCS-MC, a Monte-Carlo based algorithm, and predict their binding conformation as well as approximate binding affinities for the target. Here we report development of SILCS and SILCS-MC protocols to be applied to RNA targets, including 5 different RNA targets and their reported small molecule binding partners. As the ion-atmosphere is critical towards the structure and dynamics of RNA tertiary structures, 100mM NaCl was added to SILCS simulations. Additionally, it is important that the Mg2+ ions bound to the RNA be included in the simulations. To facilitate this, we integrated a feature in SILCS to determine potential Mg2+ binding sites in the starting structure of the target RNA if not experimentally captured. Promising initial results indicate that the SILCS-RNA approach may significantly enhance drug discovery efforts targeting RNAs with small molecules.