Sequential collapse folding pathway of staphylococcal nuclease: Entropic activation barriers to hydrophobic collapse of the protein core

In this paper the sequential collapse model (SCM) is applied to reveal the folding pathway of staphylococcal nuclease. It is found that there are two energetically equivalent dominant primary contacts leading potentially to two distinct folding pathways. A third weaker contact is likely to initiate an additional less populated pathway. The findings are compared with previous theoretical and experimental results, including laboratory data suggesting that the later stages of the folding pathway of staphylococcal nuclease might be kinetically controlled. The activation barriers observed to control the intermediate stages of the folding pathway are postulated to correspond to the configurational activation barriers governing the cooperative collapse phase along each of the three predicted folding pathways.