Diffusion-collision model study of misfolding in a four-helix bundle protein.
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.
Beck
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Molecular Modeling Laboratory, Department of Physics, Tufts University, Medford, Massachussetts 02155, USA.
Siemens
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Weaver
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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