A quantum-mechanical study of the chain-length dependent stability of the extended and 3(10)-helix conformations in dehydroalanine oligopeptides.

A quantum-chemical study of the chain-length dependent stability of the extended, 2-ribbon and 3(10)-helix conformations in dehydroalanine (delta Ala) oligopeptides has been performed by using both semiempirical AM1 and ab initio 4-31G methodologies. The validity of both methods in the study of the conformational properties of delta Ala oligopeptides was tested first on the dipeptide. The results of this test showed that 4-31G and AM1 calculations are in good agreement with 6-31G* calculations and experimental data. In order to monitor the conformational conversions, delta Ala oligopeptides comprising two to six residues were constructed. Molecular geometries were fully optimized using AM1, and the final conformations were verified to be minima by analysis of the corresponding second-derivative matrices. Conformational studies revealed that the 3(10)-helix is stabilized with respect to the 2(7)-ribbon when the number of residues is three or four, at the AM1 and ab initio 4-31G level respectively, while the extended form is the most stable in all the calculations performed. On the other hand, if a linear behaviour is assumed for longer chains, our calculations show a trend that would predict a conversion from extended form to 3(10)-helix in oligopeptides with around six (ab initio 4-31G) or eight (AM1) delta Ala residues. In order to explain these conformational changes, the cooperative effects for the different conformers were investigated. Large cooperative energy effects were found for the 3(10)-helix conformation.