Exploring Protein Supersecondary Structure Through Changes in Protein Folding, Stability, and Flexibility

Methods Mol Biol. 2019:1958:173-185. doi: 10.1007/978-1-4939-9161-7_9.

Abstract

The ability to predict how mutations affect protein structure, folding, and flexibility can elucidate the molecular mechanisms leading to disruption of supersecondary structures, the emergence of phenotypes, as well guiding rational protein engineering. The advent of fast and accurate computational tools has enabled us to comprehensively explore the landscape of mutation effects on protein structures, prioritizing mutations for rational experimental validation.Here we describe the use of two complementary web-based in silico methods, DUET and DynaMut, developed to infer the effects of mutations on folding, stability, and flexibility and how they can be used to explore and interpret these effects on protein supersecondary structures.

Keywords: DUET; DynaMut; Graph-based signatures; Machine learning; Missense mutations; Normal mode analysis; Protein stability and folding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Substitution / genetics*
  • Computational Biology / methods*
  • Humans
  • Mutation, Missense / genetics
  • Protein Engineering / methods*
  • Protein Folding
  • Protein Stability
  • Proteins / chemistry*
  • Proteins / genetics

Substances

  • Proteins