Non-native interactions in protein folding intermediates: molecular dynamics simulations of hen lysozyme.
Molecular dynamics simulations of protein denaturation can complement and extend experimental studies of protein folding by providing atomic-level structural 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 unfolded alpha-domain and a structured beta-domain, which is inconsistent with experiment. In contrast, the beta-domain unfolded first in the two simulations presented here leaving a structured alpha-domain. Following this, intermediate states were identified that differ with respect to the packing of the helices and the elements of non-native structure adopted. The non-native structure is critical for explaining many of the experimental observations. Overall, the pooled ensemble of these intermediates is in agreement with the experimental data for the major kinetic intermediate, suggesting that the kinetic intermediate may be made up of distinct, but rapidly interconverting, partially folded conformations distinguished primarily by differences in helix packing.
Kazmirski
S L
SL
Department of Medicinal Chemistry, University of Washington, Seattle, WA, 98195-7610, USA.
Daggett
V
V
D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D005260:Female; D007700:Kinetics; D008969:Molecular Sequence Data; D009113:Muramidase / Q000737:chemistry*; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding
D009113:Muramidase