Conformational-analysis and structural study by ab-initio gradient geometry optimizations of the model tripeptide n-formyl l-alanyl l-alanine amide
Faculty of Sciences. Chemistry
Theochem: applications of theoretical chemistry to organic, inorganic and biological problems. - Amsterdam, 1981 - 2010
, p. 149-163
University of Antwerp
The geometries of 15 conformations of the model tripeptide N-formyl L-alanyl L-alanine amide (Ala-Ala) were determined by ab initio gradient geometry refinements at the HF/4-21G level. The results can be compared with previous HF/4-21G calculations on the single residue, N-formyl alanine amide (Ala), and the model hexapeptide, N-formyl pentaalanine amide (Penta-Ala). Cooperative energy effects are found in Ala-Ala that are subtle in some (phi1, psi1 and phi2, psi2) conformations, such as (C7eq, C7ax), (beta, C7eq) and (C7ax, C7ax), but more pronounced in bend forms, such as (C7eq, alpha'), (C7eq, alpha(L)), and (C7ax, 3/10). Optimization of alpha-helical structures leads to 3/10-type helices, both in empirical CHARMm and ab initio HF/4-21G calculations, away from alpha(R). This property of the calculated vacuum structures is in agreement with experimental investigations of short alanine based peptides in aqueous solution. The conformationally dependent structural trends found here for Ala-Ala are in agreement with the trends previously derived for Ala and Penta-Ala. They are particularly significant for the N-C(alpha)-C' angle. This parameter shows variations of up to 8-degrees in the selected conformers and, regardless of how the residues are combined, its extension follows the approximate sequence beta < C7eq < C7ax almost-equal-to 3/10-helix.