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Computational design of a symmetric homodimer using ?-strand assembly.

ABSTRACT: Computational design of novel protein-protein interfaces is a test of our understanding of protein interactions and has the potential to allow modification of cellular physiology. Methods for designing high-affinity interactions that adopt a predetermined binding mode have proved elusive, suggesting the need for new strategies that simplify the design process. A solvent-exposed backbone on a ?-strand is thought of as "sticky" and ?-strand pairing stabilizes many naturally occurring protein complexes. Here, we computationally redesign a monomeric protein to form a symmetric homodimer by pairing exposed ?-strands to form an intermolecular ?-sheet. A crystal structure of the designed complex closely matches the computational model (rmsd = 1.0 Å). This work demonstrates that ?-strand pairing can be used to computationally design new interactions with high accuracy.

SUBMITTER: Stranges PB

PROVIDER: S-EPMC3251150 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Computational design of a symmetric homodimer using β-strand assembly.

Stranges P Benjamin PB Machius Mischa M Miley Michael J MJ Tripathy Ashutosh A Kuhlman Brian B

Proceedings of the National Academy of Sciences of the United States of America 20111205 51

Computational design of novel protein-protein interfaces is a test of our understanding of protein interactions and has the potential to allow modification of cellular physiology. Methods for designing high-affinity interactions that adopt a predetermined binding mode have proved elusive, suggesting the need for new strategies that simplify the design process. A solvent-exposed backbone on a β-strand is thought of as "sticky" and β-strand pairing stabilizes many naturally occurring protein compl ...[more]

PMID: 22143762

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