Biophys J, December 2001, p. 3105-3115, Vol. 81, No. 6

Diffusion-Collision Model Study of Misfolding in a Four-Helix Bundle Protein

Molecular Modeling Laboratory, Department of Physics, Tufts University, Medford, Massachussetts 02155 USA

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.

Biophys J, December 2001, p. 3105-3115, Vol. 81, No. 6
© 2001 by the Biophysical Society   0006-3495/01/12/3105/11  $2.00

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