Transition state contact orders correlate with protein folding rates.
We have used molecular dynamics simulations restrained by experimental phi values derived from protein engineering experiments to determine the structures of the transition state ensembles of ten proteins that fold with two-state kinetics. For each of these proteins we then calculated the average contact order in the transition state ensemble and compared it with the corresponding experimental folding rate. The resulting correlation coefficient is similar to that computed for the contact orders of the native structures, supporting the use of native state contact orders for predicting folding rates. The native contacts in the transition state also correlate with those of the native state but are found to be about 30% lower. These results show that, despite the high levels of heterogeneity in the transition state ensemble, the large majority of contributing structures have native-like topologies and that the native state contact order captures this phenomenon.
Paci
Emanuele
E
Institute of Molecular Biophysics and Physics & Astronomy, University of Leeds, Leeds LS2 9JT, UK.
Lindorff-Larsen
Kresten
K
Dobson
Christopher M
CM
Karplus
Martin
M
Vendruscolo
Michele
M
D007700:Kinetics; D008958:Models, Molecular; D011489:Protein Denaturation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
D011506:Proteins