Role of topology in the cooperative collapse of the protein core in the sequential collapse model. Folding pathway of α-lactalbumin and hen lysozyme

This paper further explores the recently proposed sequential collapse model (SCM) for protein folding pathways. Two specific items are considered within the SCM: (a) the cooperative collapse phase for protein folding pathways and (b) applications of the model to suggest the folding pathways of a-lactalbumin and hen lysozyme. With regard to the first goal, it is shown that major topological rearrangements of the protein core after the hydrophobic collapse are entropically unfavorable, suggesting that the final native structure is attained sequentially through a limited number of nativelike optimization steps. It is also shown that cross-links between protein loops are entropically unfavorable. This result suggests that long proteins fold in independent folding units, with each one of them corresponding to initially forming a single loop defined by a hydrophobic contact. The second objective of this paper is to illustrate further the predictive capabilities of the SCM through its application to the folding pathways of a-lactalbumin and hen lysozyme in comparison with available experimental data and previous theoretical results. It is found that the predicted folding pathways are similar for both proteins.