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Mutation-induced fold switching among lattice proteins.

Holzgräfe, Christian LU ; Irbäck, Anders LU and Troein, Carl LU (2011) In Journal of Chemical Physics 135(19).
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Chemical Physics
volume
135
issue
19
publisher
American Institute of Physics
external identifiers
  • wos:000297473300041
  • pmid:22112098
  • scopus:81855184951
ISSN
0021-9606
DOI
10.1063/1.3660691
language
English
LU publication?
yes
id
098e3262-7aa6-4417-9bec-693c2213fe3f (old id 2220431)
date added to LUP
2011-12-05 08:51:48
date last changed
2017-07-02 03:23:59
@article{098e3262-7aa6-4417-9bec-693c2213fe3f,
  abstract     = {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.},
  articleno    = {195101},
  author       = {Holzgräfe, Christian and Irbäck, Anders and Troein, Carl},
  issn         = {0021-9606},
  language     = {eng},
  number       = {19},
  publisher    = {American Institute of Physics},
  series       = {Journal of Chemical Physics},
  title        = {Mutation-induced fold switching among lattice proteins.},
  url          = {http://dx.doi.org/10.1063/1.3660691},
  volume       = {135},
  year         = {2011},
}