Despite the wealth of data on RNA secondary structure, conformational dynamics and tertiary structure in vitro and in vivo, predicting RNA biological activity in cellular environments remains difficult. Here, we present a comparison between in silico RNA fingerprinting and published experimental data that sheds light on efficient design of the hammerhead ribozyme molecules with a high intracellular efficiency. Our method, which we call RNA dactyloscopy, is a reliable tool for assessing the catalytic properties, modeling and design of RNA.