A new formalism for calculation of the partition function of single   stranded nucleic acids
  A new formalism for calculation of the partition function of single stranded nucleic acids is presented. Secondary structures and the topology of structure elements are the level of resolution that is used. The folding model deals with matches, mismatches, symmetric and asymmetric interior loops, stacked pairs in loop and dangling end regions, multi-branched loops, bulges and single base stacking that might exist at duplex ends or at the ends of helices. Calculations on short and long sequences show, that for short oligonucleotides, a duplex formation often displays a two-state transition. However, for longer oligonucleotides, the thermodynamic properties of the single self-folding transition affects the transition nature of the duplex formation, resulting in a population of intermediate hairpin species in the solution. The role of intermediate hairpin species is analyzed in the case when a short oligonucleotides (molecular beacons) have to reliably identify and hybridize to accessible nucleotides within their targeted mRNA sequences. It is shown that the enhanced specificity of the molecular beacons is a result of their constrained conformational flexibility and the all-or-none mechanism of their hybridization to the target sequence. 
Roumen A. Dimitrov