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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2220431
- author
- Holzgräfe, Christian
LU
; Irbäck, Anders
LU
and Troein, Carl
LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Chemical Physics
- volume
- 135
- issue
- 19
- article number
- 195101
- publisher
- American Institute of Physics (AIP)
- external identifiers
-
- wos:000297473300041
- pmid:22112098
- scopus:81855184951
- pmid:22112098
- 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
- 2016-04-01 11:06:16
- date last changed
- 2023-01-02 18:39:23
@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.}},
author = {{Holzgräfe, Christian and Irbäck, Anders and Troein, Carl}},
issn = {{0021-9606}},
language = {{eng}},
number = {{19}},
publisher = {{American Institute of Physics (AIP)}},
series = {{Journal of Chemical Physics}},
title = {{Mutation-induced fold switching among lattice proteins.}},
url = {{http://dx.doi.org/10.1063/1.3660691}},
doi = {{10.1063/1.3660691}},
volume = {{135}},
year = {{2011}},
}