An approach is described for predicting peptide nucleic acid (PNA):DNA duplex stability from base sequence by approximating the total free energy of dissociation, ΔG°(tot), for these duplexes as the sum of five parameters: (a) a nearest-neighbor interaction summation term, ΣN(j)ΔG°(j); (b) an initiation term, ΔG°(i); (c) a dangling-end stabilization term, ΔG°(e); (d) a PNA:DNA stabilization term per nearest-neighbor interaction, ΔG°(pna); and (e) an ionic strength term, ΔG°(Na). Parameters (a) and (b) are approximated using previously determined values for DNA:DNA duplexes, whereas parameters (c), (d), and (e) are empirically determined. These terms are used to calculate ΔG°(tot), which is used in conjunction with a transition enthalpy (ΔH°) value, also approximated from nearest-neighbor values previously derived for DNA:DNA duplexes, to calculate a melting temperature (T(m)) for the PNA:DNA duplex. Predicted T(m) values calculated by this approach agreed fairly well with measured values for 11 different PNA:DNA duplexes, as well as with literature values. The approach also accurately models ionic strength effects.
Bibliographical noteFunding Information:
1T.J.G. is supported by Department of Energy Grant DE-FG02-91ER61130. 2Abbreviations used: PNA, peptide nucleic acid; MALDI, matrix-assisted laser desorption ionization.