In this paper, the sequential collapse model (SCM) for revealing protein folding pathways is applied to bovine β-lactoglobulin. The results for the dominant folding pathway are in general agreement with recent experimental data. An analysis based on the SCM suggests that, in addition to the dominant early intermediate specified by the best predicted primary contact, there are coexisting populations of early intermediates defined by the formation of less energetically favorable primary contacts. The issue of parallel folding pathways defined by primary contacts with different formation propensities is discussed. The main primary contact is energetically dominant with respect to the additional primary contacts. However, it is possible that the additional population of contacts might contribute to the non-native helical structure observed to accumulate in the early folding stages if there were kinetic constraints along the dominant pathway that led to an accumulation of misfolded early intermediates. A mutation experiment is suggested to reveal whether any non-native secondary structure contributes to the observed helical excess due to the additional folding pathways defined by the nondominant primary contacts. The relevance of these results to larger issues of protein folding is also discussed.
All Science Journal Classification (ASJC) codes
- Physical and Theoretical Chemistry
- Surfaces, Coatings and Films
- Materials Chemistry