HELIX-COIL TRANSITION THEORIES - ARE THEY CORRECT

Principles of contemporary theoretical description of a-helix formatio n by polypeptide chains in water solution are shortly presented and cr itically discussed. The theory treats the unfolded state of a peptide as ''random coil'' - an ideal conformation quite distant from reality. We suggest that for this reason the helix propagation parameters of a mino-acid residues, determined using series of model peptides with dif ferent sequential patterns, are not the same. Interpretation of the so called ''nucleation parameter'' is erroneous. In fact, it is not dete rmined by the helix nucleation process but rather by a specific situat ion of residues at the helix N- and C-termini, and it strongly depends on solvation of their NH and CO groups, respectively. Consequently, h elical segments with terminal sequences dominated by residues with str ongly hydrophobic, bulky side chains can be very unstable. We postulat e that an unexpectedly high stability of very short, pre-nucleated hel ices studied by us arises from a ''helix end separation effect'': sepa rated helix termini are better solvated than when they overlap each ot her. Because of this effect, helix initiation may be much more difficu lt than predicted by the theoretical ''helix nucleation parameters''.