Abstract

Estimates have been made of the main contributions of the heterocyclic bases of DNA to the free energies of the two configurations in solution, the two-stranded helix and the single-strand random coil. The magnitude and directions of the dipole moments of the adenine, thymine, guanine and cytosine base groups have been calculated by a semi-empirical molecular orbital treatment. Dipole—dipole, dipole—induced-dipole and London force interactions among the bases in the helix are large, and make the free energy of the helix depend on the base composition and sequence. The helix stability (helix negative free energy) is proportional to the guanine + cytosine content. A comparison of calculated base-pair interactions with the nearest-neighbor base frequency data of Josse, Kaiser & Kornberg (1961) suggests that the base sequence in natural DNA may be influenced by the free energy. The free energy of the coil is difficult to estimate ; it tends to be more negative from base—solvent interactions for a greater guanine—cytosine content. The choice of solvent determines the magnitude of these interactions and thus determines how the melting temperature of the helix will depend on the base composition. In a solvent such as water, in which significant base—base interactions exist in the coil, the coil free energy depends on the base sequence and London forces may cause stacking of the bases into ordered arrays. The hydrogen bond energy of the bases and the strain energy in the helix probably contribute little to the enthalpy change of the helix—coil transition, although they ensure specific base-pairing in the helix. The net contribution of configurational and solvent entropy changes to the free energy change of the helix—coil transition is also probably small.