Design of structurally distinct proteins using strategies inspired by evolution

Jacobs, T. M.; Williams, B.; Williams, T.; Xu, X.; Eletsky, A.; Federizon, J. F.; Szyperski, T.; Kuhlman, B.

doi:10.1126/science.aad8036

Title: Design of structurally distinct proteins using strategies inspired by evolution

Journal Article · Fri May 06 00:00:00 EDT 2016 · Science

DOI:https://doi.org/10.1126/science.aad8036· OSTI ID:1253788

Jacobs, T. M. ^[1]; Williams, B. ^[2]; Williams, T. ^[2]; Xu, X. ^[3]; Eletsky, A. ^[3]; Federizon, J. F. ^[4]; Szyperski, T. ^[4]; Kuhlman, B. ^[5]

Univ. of North Carolina, Chapel Hill, NC (United States). Program in Bioinformatics and Computational Biology
Univ. of North Carolina, Chapel Hill, NC (United States). Dept. of Biochemistry and Biophysics
Univ. at Buffalo, NY (United States). Dept. of Chemistry. Northeast Structural Genomics Consortium
Univ. at Buffalo, NY (United States). Dept. of Chemistry
Univ. of North Carolina, Chapel Hill, NC (United States). Dept. of Biochemistry and Biophysics. Lineberger Comprehensive Cancer Center

Natural recombination combines pieces of preexisting proteins to create new tertiary structures and functions. In this paper, we describe a computational protocol, called SEWING, which is inspired by this process and builds new proteins from connected or disconnected pieces of existing structures. Helical proteins designed with SEWING contain structural features absent from other de novo designed proteins and, in some cases, remain folded at more than 100°C. High-resolution structures of the designed proteins CA01 and DA05R1 were solved by x-ray crystallography (2.2 angstrom resolution) and nuclear magnetic resonance, respectively, and there was excellent agreement with the design models. Finally, this method provides a new strategy to rapidly create large numbers of diverse and designable protein scaffolds.

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Research Organization:: University of North Carolina, Chapel Hill, NC (United States); Univ. at Buffalo, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health (NIH) (United States)

Grant/Contract Number:: W-31-109-Eng-38; R01GM073960; R01GM117968; GM094597

OSTI ID:: 1253788

Journal Information:: Science, Vol. 352, Issue 6286; ISSN 0036-8075

Publisher:: AAASCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 94 works

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