An approach to predicting the stabilities of peptide nucleic acid:DNA duplexes

An approach is described for predicting peptide nucleic acid (PNA):DNA duplex stability from base sequence by approximating the total free energy of dissociation, Delta G degrees(tot), for these duplexes as the sum of five parameters: (a) a nearest-neighbor interaction summation term, Sigma N(j)Delta G degrees(j); (b) an initiation term, Delta G degrees(i); (c) a dangling-end stabilization term, Delta G degrees(e); (d) a PNA:DNA stabilization term per nearest-neighbor interaction, Delta G degrees(pna); and (e) an ionic strength term, Delta G degrees(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 Delta G degrees(tot),which is used in conjunction with a transition enthalpy (Delta H degrees) 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. (C) 1998 Academic Press.