Leipzig

Abstract: A systematic analysis of the substituent influence on the formation of the unique secondary structure type of ‘‘mixed’ ’ helices in the homologous -, -, and -peptides was performed on the basis of ab initio molecular orbital theory. Contrary to the common periodic peptide helices, mixed helices have an alternating periodicity and their hydrogen-bonding pattern is similar to those of -sheets. They belong, therefore, to the family of -helices. It is shown that folding of peptide sequences into mixed heli-ces is energetically preferred over folding into their periodic counterparts in numerous cases. The influ-ence of entropy and solvents on the formation of the various competitive mixed and periodic helix types is discussed. Among the oligomers of the various homologous amino acids, -peptides show the highest tendency to form -helices. The rules of substituent influence derived from the analysis of a wide vari-ety of backbone substitution patterns might be helpful for a rational design of mixed helix structures, which could be important for mimicking membrane channels. # 2005 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 80: 675–687, 2005 This article was originally published online as an accepted preprint. The ‘‘Published Online’ ’ date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office a