TY - JOUR

T1 - Transition State Contact Orders Correlate with Protein Folding Rates

AU - Paci, Emanuele

AU - Lindorff-Larsen, K.

AU - Dobson, Christopher M.

AU - Karplus, Martin

AU - Vendruscolo, Michele

N1 - Keywords: contact order; transition states; protein folding

PY - 2005

Y1 - 2005

N2 - We have used molecular dynamics simulations restrained by experimental 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.

AB - We have used molecular dynamics simulations restrained by experimental 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.

U2 - 10.1016/j.jmb.2005.06.081

DO - 10.1016/j.jmb.2005.06.081

M3 - Journal article

C2 - 16120445

VL - 352

SP - 495

EP - 500

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 3

ER -