Rational design of temperature-sensitive alleles using computational structure prediction

Christopher S. Poultney, Glenn L. Butterfoss, Michelle R. Gutwein, Kevin Drew, David Gresham, Kristin C. Gunsalus, Dennis E. Shasha, Richard Bonneau

Research output: Contribution to journalArticle

Abstract

Temperature-sensitive (ts) mutations are mutations that exhibit a mutant phenotype at high or low temperatures and a wild-type phenotype at normal temperature. Temperature-sensitive mutants are valuable tools for geneticists, particularly in the study of essential genes. However, finding ts mutations typically relies on generating and screening many thousands of mutations, which is an expensive and labor-intensive process. Here we describe an in silico method that uses Rosetta and machine learning techniques to predict a highly accurate "top 5" list of ts mutations given the structure of a protein of interest. Rosetta is a protein structure prediction and design code, used here to model and score how proteins accommodate point mutations with side-chain and backbone movements. We show that integrating Rosetta relax-derived features with sequence-based features results in accurate temperature-sensitive mutation predictions.

Original languageEnglish (US)
Article numbere23947
JournalPLoS One
Volume6
Issue number9
DOIs
StatePublished - Sep 2 2011

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Alleles
alleles
Temperature
prediction
mutation
Mutation
temperature
protein structure
Phenotype
phenotype
mutants
geneticists
Proteins
artificial intelligence
Essential Genes
point mutation
Point Mutation
Computer Simulation
Learning systems
Screening

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Rational design of temperature-sensitive alleles using computational structure prediction. / Poultney, Christopher S.; Butterfoss, Glenn L.; Gutwein, Michelle R.; Drew, Kevin; Gresham, David; Gunsalus, Kristin C.; Shasha, Dennis E.; Bonneau, Richard.

In: PLoS One, Vol. 6, No. 9, e23947, 02.09.2011.

Research output: Contribution to journalArticle

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