Abstract
Helices represent one of the most common recognition motifs in proteins. The design of nonpeptidic scaffolds, such as the 3,2′,2″‐tris‐substituted terphenyl, that can imitate the side‐chain orientation along one face of an α‐helix potentially provides an effective means to modulate helix‐recognition functions. Here, based on theoretical arguments, we described novel α‐helix mimetics which are more effective than the terphenyl at constraining the aryl–aryl torsion angles to those associated with structures suitable for mimicking the α‐helical twist for side‐chain orientation and for superimposing the side chains of residues i, i + 3 or i + 4, i + 7 when compared with the α–β side‐chain vectors of the regular α‐helix with an improved root mean square deviation (RMSD) of approximately 0.5 Å. In addition, this study suggests that rotamer distributions around the C~α~C~β~ bonds of these helix mimetics are similar to those of α‐helices, except that these rotamer distributions show an approximately 60° shift compared to those of α‐helices when the mimetic axis is superimposed upon the helix axis. This change in rotamer orientation complicates mimicry of the helix surface. © 2007 Wiley Periodicals, Inc. Biopolymers 86: 288–297, 2007.
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