Sl. Kazmirski et V. Daggett, Non-native interactions in protein folding intermediates: Molecular dynamics simulations of hen lysozyme, J MOL BIOL, 284(3), 1998, pp. 793-806
Molecular dynamics simulations of protein denaturation can complement and e
xtend experimental studies of protein folding by providing atomic-level str
uctural information about conformational transitions and any conformational
states along the unfolding pathway. Previous unfolding simulations of hen
egg-white lysozyme have resulted in intermediate structures with an unfolde
d alpha-domain and a structured beta-domain, which is inconsistent with exp
eriment. In contrast, the beta-domain unfolded first in the two simulations
presented here leaving a structured alpha-domain. Following this, intermed
iate states were identified that differ with respect to the packing of the
helices and the elements of non-native structure adopted. The non-native st
ructure is critical for explaining many of the experimental observations. O
verall, the pooled ensemble of these intermediates is in agreement with the
experimental data for the major kinetic intermediate, suggesting that die
kinetic intermediate may be made up of distinct, but rapidly interconvertin
g, partially folded conformations distinguished primarily by differences in
helix packing. (C) 1998 Academic Press.