Abstract
In order to check our current knowledge on the principles involved in β‐hairpin formation, we have modified the sequence of a 3:5 β‐hairpin forming peptide with two different purposes, first to increase the stability of the formed 3:5 β‐hairpin, and second to convert the 3:5 β‐hairpin into a 2:2 β‐hairpin. The conformational behavior of the designed peptides was investigated in aqueous solution and in 30% trifluoroethanol (TFE) by analysis of the following nuclear magnetic resonance (NMR) parameters: nuclear Overhauser effect (NOE) data, and C~α~H, ^13^C~α~, and ^13^C~β~ conformational shifts. From the differences in the ability to adopt β‐hairpin structures in these peptides, we have arrived to the following conclusions: (i) β‐Hairpin population increases with the statistical propensity of residues to occupy each turn position. (ii) The loop length, and in turn, the β‐hairpin type, can be modified as a function of the type of turn favored by the loop sequence. These two conclusions reinforce previous results about the importance of β‐turn sequence in β‐hairpin folding. (iii) Side‐chain packing on each face of the β‐sheet may play a major role in β‐hairpin stability; hence simplified analysis in terms of isolated pair interactions and intrinsic β‐sheet propensities is insufficient. (iv) Contributions to β‐hairpin stability of turn and strand sequences are not completely independent. (v) The burial of hydrophobic surface upon β‐hairpin formation that, in turn, depends on side‐chain packing also contributes to β‐hairpin stability. (vi) As previously observed, TFE stabilizes β‐hairpin structures, but the extent of the contribution of different factors to β‐hairpin formation is sometimes different in aqueous solution and in 30% TFE. © 2005 Wiley Periodicals, Inc. Biopolymers 79: 150–162, 2005
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