In vitro selection is a versatile experimental tool for discovering novel synthetic RNAs. However, most RNAs identified from random sequence pools are small and simple folding motifs. To significantly increase the probability of discovering novel RNAs, we develop an approach for engineering sequence pools that links RNA sequence space regions with corresponding structural distributions via a "mixing matrix" approach combined with a graph theory analysis of RNA 2D structure space. Our pool design method has been automated and made available through the web server RAGPOOLS (http://rubin2.biomath.nyu.edu). The RAGPOOLS serves as a guide to researchers who aim to synthesize RNA pools with desired properties and/or experiment in silico with various designs by our approach.