A general computational approach for repeat protein design

Fabio Parmeggiani, Po-Ssu Huang, Sergey Vorobiev, Rong Xiao, Keunwan Park, Silvia Caprari, Min Su, Jayaraman Seetharaman, Lei Mao, Haleema Janjua, Gaetano T Montelione, John Hunt, David Baker

Research output: Contribution to journalArticle (Academic Journal)

51 Citations (Scopus)

Abstract

Repeat proteins have considerable potential for use as modular binding reagents or biomaterials in biomedical and nanotechnology applications. Here we describe a general computational method for building idealized repeats that integrates available family sequences and structural information with Rosetta de novo protein design calculations. Idealized designs from six different repeat families were generated and experimentally characterized; 80% of the proteins were expressed and soluble and more than 40% were folded and monomeric with high thermal stability. Crystal structures determined for members of three families are within 1Å root-mean-square deviation to the design models. The method provides a general approach for fast and reliable generation of stable modular repeat protein scaffolds.

Original languageEnglish
Pages (from-to)563-75
Number of pages13
JournalJournal of Molecular Biology
Volume427
Issue number2
DOIs
Publication statusPublished - 30 Jan 2015

Structured keywords

  • Bristol BioDesign Institute

Keywords

  • Amino Acid Sequence
  • Ankyrins
  • Armadillo Domain Proteins
  • Biocompatible Materials
  • Computer Simulation
  • Crystallography, X-Ray
  • Microfilament Proteins
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Protein Conformation
  • Protein Engineering
  • Proteins
  • Sequence Alignment
  • Sequence Analysis, Protein
  • synthetic biology

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  • Cite this

    Parmeggiani, F., Huang, P-S., Vorobiev, S., Xiao, R., Park, K., Caprari, S., Su, M., Seetharaman, J., Mao, L., Janjua, H., Montelione, G. T., Hunt, J., & Baker, D. (2015). A general computational approach for repeat protein design. Journal of Molecular Biology, 427(2), 563-75. https://doi.org/10.1016/j.jmb.2014.11.005