RT Journal Article
SR Electronic
T1 High-Resolution Protein Design with Backbone Freedom
JF Science
JO Science
FD American Association for the Advancement of Science
SP 1462
OP 1467
DO 10.1126/science.282.5393.1462
VO 282
IS 5393
A1 Harbury, Pehr B.
A1 Plecs, Joseph J.
A1 Tidor, Bruce
A1 Alber, Tom
A1 Kim, Peter S.
YR 1998
UL http://science.sciencemag.org/content/282/5393/1462.abstract
AB Recent advances in computational techniques have allowed the design of precise side-chain packing in proteins with predetermined, naturally occurring backbone structures. Because these methods do not model protein main-chain flexibility, they lack the breadth to explore novel backbone conformations. Here the de novo design of a family of α-helical bundle proteins with a right-handed superhelical twist is described. In the design, the overall protein fold was specified by hydrophobic-polar residue patterning, whereas the bundle oligomerization state, detailed main-chain conformation, and interior side-chain rotamers were engineered by computational enumerations of packing in alternate backbone structures. Main-chain flexibility was incorporated through an algebraic parameterization of the backbone. The designed peptides form α-helical dimers, trimers, and tetramers in accord with the design goals. The crystal structure of the tetramer matches the designed structure in atomic detail.