TitleDesignability of alpha-helical proteins.
Publication TypeJournal Article
Year of Publication2002
AuthorsEmberly, EG, Wingreen, NS, Tang, C
JournalProc Natl Acad Sci U S A
Date Published2002 Aug 20
KeywordsAmino Acid Sequence, Databases, Protein, Drug Design, Models, Molecular, Protein Structure, Secondary, Protein Structure, Tertiary, Proteins

A typical protein structure is a compact packing of connected alpha-helices and/or beta-strands. We have developed a method for generating the ensemble of compact structures a given set of helices and strands can form. The method is tested on structures composed of four alpha-helices connected by short turns. All such natural four-helix bundles that are connected by short turns seen in nature are reproduced to closer than 3.6 A per residue within the ensemble. Because structures with no natural counterpart may be targets for ab initio structure design, the designability of each structure in the ensemble-defined as the number of sequences with that structure as their lowest-energy state-is evaluated using a hydrophobic energy. For the case of four alpha-helices, a small set of highly designable structures emerges, most of which have an analog among the known four-helix fold families; however, several packings and topologies with no analogs in protein database are identified.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.