SH3 Domain Unfolding Pathway Studied by Protein Contact Network Model

The approach of complex networks has provided one powerful tool to understand how proteins consistently fold into their native-state structures and the relevance of structure to their function. In this study, a coarse-grained complex network model called Protein Contact Network (PCN) is employed to study the unfolding process of SH3 domain, and the change of the network parameters associated with the conformational changes was analyzed on the SH3 unfolding pathway. The results show that the average clustering coefficient is less sensitive to the structural change, however the average shortest path lengths can examine the larger structural changes. Betweenness parameters, which characterize the geometrical properties of hydrophobic cores and folding nucleus residues, are shown out by the significant maximum values of native and transition state in the networks, respectively. It is easy to distinguish the folding nucleus from other residues by the betweenness of the transition state network, and it is easy to identify the hydrophobic core regions with the betweenness of the native state network. The results indicate that the unfolding of SH3 is mainly exhibited as the decrease of the long-rang links, and both the hydrophobic core and folding nucleus of the protein become derogated from its native state to the denature state. The hydrophobic collapse model and nucleation condensation model become reconciled in this work.