A novel, multilayer structure of a helical peptide

X‐ray diffraction analysis at 1.5 A resolution has confirmed the helical conformation of a de novo designed 18‐residue peptide. However, the crystal structure reveals the formation of continuous molecular layers of parallel‐packed amphiphilic helices as a result of much more extensive helix‐helix interactions than predicted. The crystal packing arrangement, by virtue of distinct antiparallel packing interactions, segregates the polar and apolar surfaces of the helices into discrete and well‐defined interfacial regions. An extensive “ridges‐into‐grooves” interdigitation characterizes the hydrophobic interface, whereas an extensive network of salt bridges and hydrogen bonds dominates the corresponding hydrophilic interface.