Format

Send to

Choose Destination
Science. 2016 May 6;352(6286):687-90. doi: 10.1126/science.aad8036.

Design of structurally distinct proteins using strategies inspired by evolution.

Author information

1
Program in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
2
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
3
Department of Chemistry, State University of New York at Buffalo, Buffalo, NY 14260, USA. Northeast Structural Genomics Consortium.
4
Department of Chemistry, State University of New York at Buffalo, Buffalo, NY 14260, USA.
5
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. bkuhlman@email.unc.edu.

Abstract

Natural recombination combines pieces of preexisting proteins to create new tertiary structures and functions. 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. This method provides a new strategy to rapidly create large numbers of diverse and designable protein scaffolds.

Comment in

PMID:
27151863
PMCID:
PMC4934125
DOI:
10.1126/science.aad8036
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center