Evolution-based design of proteins

Kimberly A. Reynolds, William P. Russ, Michael Socolich, Rama Ranganathan

Research output: Chapter in Book/Report/Conference proceedingChapter

23 Scopus citations

Abstract

Statistical analysis of protein sequences indicates an architecture for natural proteins in which amino acids are engaged in a sparse, hierarchical pattern of interactions in the tertiary structure. This architecture might be a key and distinguishing feature of evolved proteins - a design principle providing not only for foldability and high-performance function but also for robustness to perturbation and the capacity for rapid adaptation to new selection pressures. Here, we describe an approach for systematically testing this design principle for natural-like proteins by (1) computational design of synthetic sequences that gradually add or remove constraints along the hierarchy of interacting residues and (2) experimental testing of the designed sequences for folding and biochemical function. By this process, we hope to understand how the constraints on fold, function, and other aspects of fitness are organized within natural proteins, a first step in understanding the process of "design" by evolution.

Original languageEnglish (US)
Title of host publicationMethods in Protein Design
PublisherAcademic Press Inc.
Pages213-235
Number of pages23
ISBN (Print)9780123942920
DOIs
StatePublished - 2013

Publication series

NameMethods in Enzymology
Volume523
ISSN (Print)0076-6879
ISSN (Electronic)1557-7988

Keywords

  • Evolution
  • Folding
  • Protein design
  • SCA
  • Sector

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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    Reynolds, K. A., Russ, W. P., Socolich, M., & Ranganathan, R. (2013). Evolution-based design of proteins. In Methods in Protein Design (pp. 213-235). (Methods in Enzymology; Vol. 523). Academic Press Inc.. https://doi.org/10.1016/B978-0-12-394292-0.00010-2