What is the rationale of Sfold target-accessibility prediction for the design of RNA-targeting nucleic acids?
• Our prediction of accessibility is based on a statistical sample of the Boltzmann ensemble of secondary structures. This novel approach is appealing for evaluation of target accessibility, because, as noted by researchers from Sirna Therapeutics (formerly Ribozyme Pharmaceuticals, Inc.), “In the prediction of accessible sites, the identification of a single folded structure for a given target mRNA is not of particular interest. Instead, the objective of this exercise is to assess the likelihood of unpaired (or substantially unpaired) sites that could be a ribozyme target… The ambiguities in thermodynamic parameters – and the possibility that each mRNA exists as a population of different structures – suggest that a stochastic approach to the evaluation of accessible sites may be appropriate” (Christoffersen, McSwiggen & Konings 1994, J. Mol. Structure (Theochem) 311, p. 208). The probability profiling approach in Ding and Lawrence (2001, Nucleic Acids Res. 29, 1034-1046.) reveals ta
