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dc.contributor.authorKaranicolas, John
dc.contributor.authorCorn, Jacob E.
dc.contributor.authorChen, Irwin
dc.contributor.authorJoachimiak, Lukasz A.
dc.contributor.authorDym, Orly
dc.contributor.authorPeck, Sun H.
dc.contributor.authorAlbeck, Shira
dc.contributor.authorUnger, Tamar
dc.contributor.authorHu, Wenxin
dc.contributor.authorLiu, Gaohua
dc.contributor.authorDelbecq, Scott
dc.contributor.authorMontelione, Gaetano
dc.contributor.authorSpiegel, Clint
dc.contributor.authorLiu, David R.
dc.contributor.authorBaker, David
dc.identifier.citationKaranicolas, J., Corn, J. E., Chen, I., Joachimiak, L. A., Dym, O., Peck, S. H., … Baker, D. (2011). A de novo protein binding pair by computational design and directed evolution. Molecular Cell, 42(2), 250–260.
dc.description.abstractThe de novo design of protein-protein interfaces is a stringent test of our understanding of the principles underlying protein-protein interactions and would enable new approaches to biological and medical challenges. Here we describe a novel motif-based method to computationally design protein-protein complexes with native-like interface composition and interaction density. Using this method we designed a pair of proteins, Prb and Pdar, that heterodimerize with a Kd of 130 nM, 1,000-fold tighter than any previously designed de novo protein-protein complex. Directed evolution identified two point mutations that improve affinity to 180 pM. Crystal structures of complexes containing designed and evolved proteins reveal binding is entirely through the designed interface, making use of specific designed interactions. Surprisingly, in the evolved complex one of the partners is rotated 180 degrees relative to the design model. This work demonstrates that current understanding of protein-protein interfaces is sufficient to rationally design interfaces de novo, and underscores remaining challenges.en_US
dc.subjectComputational designen_US
dc.subjectDirected evolutionen_US
dc.subjectProtein-protein interfaceen_US
dc.subjectProtein interactionen_US
dc.subjectAnkyrin Repeaten_US
dc.subjectProtein dockingen_US
dc.titleA de novo protein binding pair by computational design and directed evolutionen_US
kusw.kuauthorKaranicolas, John
kusw.kudepartmentMolecular Biosciencesen_US
kusw.oanotesPer SHERPA/RoMEO 6/22/2017: Author's Pre-print: cross author cannot archive pre-print (ie pre-refereeing) Author's Post-print: grey tick subject to Restrictions below, author can archive post-print (ie final draft post-refereeing) Restrictions:

12 months embargo

Publisher's Version/PDF: cross author cannot archive publisher's version/PDF General Conditions:

On non-commercial hosting platforms including institutional repository Published source must be acknowledged Must link to journal homepage with DOI Publisher's version/PDF cannot be used
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US

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