Patricia L. Clark » Image Gallery

"Double Funnels" to Include Aggregation on the Folding Energy Landscape

The complexity involved in the folding of a polypeptide chain into a native protein structure is often depicted using a funnel cartoon: the broad top of the funnel represents the enormous ensemble of unfolded conformations, yet folding proceeds because the native structure is the global energy minimum (narrow bottom). Yet typical folding funnels do not include the contribution of stabilizing, off-pathway, intermolecular interactions on the folding pathway. Here, incorrect interactions leading to aggregation are included as a second, grey funnel. See Clark (2004) TiBS for more information.