Final published version
Licence: CC BY: Creative Commons Attribution 4.0 International License
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Why do protein folding rates correlate with metrics of native topology?
AU - Faísca, Patrícia F N
AU - Travasso, Rui D M
AU - Parisi, Andrea
AU - Rey, Antonio
PY - 2012/4/27
Y1 - 2012/4/27
N2 - For almost 15 years, the experimental correlation between protein folding rates and the contact order parameter has been under scrutiny. Here, we use a simple simulation model combined with a native-centric interaction potential to investigate the physical roots of this empirical observation. We simulate a large set of circular permutants, thus eliminating dependencies of the folding rate on other protein properties (e.g. stability). We show that the rate-contact order correlation is a consequence of the fact that, in high contact order structures, the contact order of the transition state ensemble closely mirrors the contact order of the native state. This happens because, in these structures, the native topology is represented in the transition state through the formation of a network of tertiary interactions that are distinctively long-ranged.
AB - For almost 15 years, the experimental correlation between protein folding rates and the contact order parameter has been under scrutiny. Here, we use a simple simulation model combined with a native-centric interaction potential to investigate the physical roots of this empirical observation. We simulate a large set of circular permutants, thus eliminating dependencies of the folding rate on other protein properties (e.g. stability). We show that the rate-contact order correlation is a consequence of the fact that, in high contact order structures, the contact order of the transition state ensemble closely mirrors the contact order of the native state. This happens because, in these structures, the native topology is represented in the transition state through the formation of a network of tertiary interactions that are distinctively long-ranged.
KW - Computer Simulation
KW - Kinetics
KW - Models, Molecular
KW - Protein Folding
KW - Protein Structure, Tertiary
KW - Proteins
KW - Thermodynamics
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1371/journal.pone.0035599
DO - 10.1371/journal.pone.0035599
M3 - Journal article
C2 - 22558173
VL - 7
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 4
M1 - e35599
ER -