The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Anders Irbäck. Photo.

Anders Irbäck

Professor

Anders Irbäck. Photo.

Mutation-induced fold switching among lattice proteins.

Author

  • Christian Holzgräfe
  • Anders Irbäck
  • Carl Troein

Summary, in English

Recent experiments uncovered a mutational pathway between two proteins, along which a single mutation causes a switch in fold. Searching for such paths between real proteins remains, despite this achievement, a true challenge. Here, we analyze fold switching in the minimalistic hydrophobic/polar model on a square lattice. For this analysis, we generate a comprehensive sequence-structure database for chains of length ≤ 30, which exceeds previous work by five units. Single-mutation-induced fold switching turns out to be quite common in the model. The switches define a fold network, whose topology is roughly similar to what one would expect for a set of randomly connected nodes. In the combinatorially challenging search for fold switches between two proteins, a tempting strategy is to only consider paths containing the minimum number of mutations. Such a restricted search fails to correctly identify 40% of the single-mutation-linked fold pairs that we observe. The thermodynamic stability is correlated with mutational stability and is, on average, markedly reduced at the observed fold switches.

Department/s

  • Computational Biology and Biological Physics

Publishing year

2011

Language

English

Publication/Series

Journal of Chemical Physics

Volume

135

Issue

19

Document type

Journal article

Publisher

American Institute of Physics (AIP)

Topic

  • Biophysics

Status

Published

ISBN/ISSN/Other

  • ISSN: 0021-9606