DFT studies on helix formation in N-acetyl-(L-alanyl)n-N′-methylamide for n=1-20

We compare the geometries and relative energies of important secondary structural elements, the 3.6(13) helix, 3(10) helix and C-5(ext) structures, for a set of blocked peptide models, N-acetyl-(L-alanyl)(n)-N'-methylamide, for n = 1-20. We use full density-functional theory (DFT) calculations at the B3LYP/6-31G* level (for peptides up toll residues), the self-consistent-charge density-functional tight binding (SCC-DFTB) and the semiempirical AM1 method. The 3.6(13) and 3(10) structures are found to be not inherently stable in general. Their stability is dependent on peptide length, other structural motifs and aqueous or membrane environments. For short peptides with less than eight residues, the 3.6(13) helix relaxes into the 3(10) structure. For longer peptides, the 3.6(13) is Stable in the middle of the chain, while the ends assume 3(10) conformations, at the C-terminus additionally a beta II type turn is formed. The relative energies and structures calculated with the recently developed SCC-DFTB method are in very good agreement with the results from the B3LYP density-functional calculations. Therefore, we use the SCC-DFTB method to look at helix formation in N-acetyl-(L-alanyl)(n)-N'-methylamide for n = 11, 14, 17 and 20. On the SCC-DFTB potential energy surface, we find the 3(10) helix to be more stable than the 3.6(13) helix for all peptide sizes. However, the effects of solution might change this picture and favor the 3.6(13) motif. (C) 2000 Elsevier Science B.V. All rights reserved.