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
SN - 0022-2836
VL - 352
SP - 495
EP - 500
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 3
ER -