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 d iffusion-collision model to study non-native kinetic intermediate misfoldin g in a four-helix bundle protein. We find a limit on the size of the pairwi se hydrophobic area loss in non-native intermediates, such that burying abo ve this limit creates long-lasting non-native kinetic intermediates that wo uld disrupt folding and prevent formation of the native state. Our study of misfolding suggests a method for limiting the production of misfolded kine tic intermediates for helical proteins and could, perhaps, lead to more eff icient production of proteins in bulk.