3u3b

Publication Abstract from PubMed

Protein design tests our understanding of protein stability and structure. Successful design methods should allow the exploration of sequence space not found in nature. However, when redesigning naturally occurring protein structures, most fixed backbone design algorithms return amino acid sequences that share strong sequence identity with wild-type sequences, especially in the protein core. This behavior places a restriction on functional space that can be explored and is not consistent with observations from nature, where sequences of low identity have similar structures. Here, we allow backbone flexibility during design to mutate every position in the core (38 residues) of a four-helix bundle protein. Only small perturbations to the backbone, 1-2 A, were needed to entirely mutate the core. The redesigned protein, DRNN, is exceptionally stable (melting point >140 degrees C). An NMR and X-ray crystal structure show that the side chains and backbone were accurately modeled (all-atom RMSD = 1.3 A).

Increasing sequence diversity with flexible backbone protein design: the complete redesign of a protein hydrophobic core.,Murphy GS, Mills JL, Miley MJ, Machius M, Szyperski T, Kuhlman B Structure. 2012 Jun 6;20(6):1086-96. Epub 2012 May 24. PMID:22632833^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.