Mutation-induced fold switching among lattice proteins.
Author
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.
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