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

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.
Authors:
 [1] ;  [2] ;  [2] ;  [3] ;  [3] ;  [4] ;  [4] ;  [5]
  1. Univ. of North Carolina, Chapel Hill, NC (United States). Program in Bioinformatics and Computational Biology
  2. Univ. of North Carolina, Chapel Hill, NC (United States). Dept. of Biochemistry and Biophysics
  3. Univ. at Buffalo, NY (United States). Dept. of Chemistry. Northeast Structural Genomics Consortium
  4. Univ. at Buffalo, NY (United States). Dept. of Chemistry
  5. Univ. of North Carolina, Chapel Hill, NC (United States). Dept. of Biochemistry and Biophysics. Lineberger Comprehensive Cancer Center
Publication Date:
OSTI Identifier:
1253788
Grant/Contract Number:
W-31-109-Eng-38; R01GM073960; R01GM117968; GM094597
Type:
Accepted Manuscript
Journal Name:
Science
Additional Journal Information:
Journal Volume: 352; Journal Issue: 6286; Journal ID: ISSN 0036-8075
Publisher:
AAAS
Research Org:
Univ. of North Carolina, Chapel Hill, NC (United States); Univ. at Buffalo, NY (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Inst. of Health (NIH) (United States)
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES