What does a rough folding funnel indicate?

A rough folding funnel indicates less cooperative folding of proteins. In the context of protein folding, a funnel-shaped energy landscape represents the energy states of a protein as it transitions from its unfolded to folded state. When the funnel is rough, it suggests that there are several local minima in the energy landscape, which indicates that the protein can get trapped in various non-native states before reaching the native conformation.

This roughness can lead to a folding process that is less cooperative because the presence of multiple energy basins means that the protein's folding pathways can vary significantly. As a result, the transitions between these states may not be synchronized or cooperative, leading to a folding process that is more chaotic and less predictable than a smoother, more cooperative folding funnel where the protein would fold through a more defined and efficient pathway. Therefore, the rough folding funnel is associated with the complexities and challenges of achieving the correctly folded protein state.