title: Diffusion-collision model study of misfolding in a four-helix bundle protein.
abstract: Proteins with complex folding kinetics will be susceptible to misfolding at some stage in the folding process. We simulate this problem by using the diffusion-collision model to study non-native kinetic intermediate misfolding in a four-helix bundle protein. We find a limit on the size of the pairwise hydrophobic area loss in non-native intermediates, such that burying above this limit creates long-lasting non-native kinetic intermediates that would disrupt folding and prevent formation of the native state. Our study of misfolding suggests a method for limiting the production of misfolded kinetic intermediates for helical proteins and could, perhaps, lead to more efficient production of proteins in bulk.
authors.affiliation: Molecular Modeling Laboratory, Department of Physics, Tufts University, Medford, Massachussetts 02155, USA.
authors.forename: C
authors.initials: C
authors.lastname: Beck
authors.forename: X
authors.initials: X
authors.lastname: Siemens
authors.forename: D L
authors.initials: DL
authors.lastname: Weaver
mesh_terms: D004058:Diffusion; D007700:Kinetics; D008962:Models, Theoretical; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012984:Software; D013997:Time Factors