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Energy landscapes for protein folding, binding, and aggregation : simple funnels and beyond


The Funneled Energy Landscape Theory is currently the most widely accepted theory of protein folding. In this dissertation, the basic concepts of the Energy Landscape Theory are introduced, highlighting some of its major successes in the studies of protein folding and binding kinetics. In particular, the focus is on an idealized native-topology based (Go-type) model that corresponds to a perfectly funneled energy landscape. This simple model has proven to accurately predict the folding mechanism of many proteins, even when simplifying approximations are made. While there exists much evidence that models based on perfectly funneled energy landscapes are sufficient in many cases, there are indications that in other cases the idealized view needs some added complexity to faithfully represent folding and binding mechanisms. By exploring experimentally studied systems where the simplest Go-type models are insufficient, new paradigms and concepts add to our current understanding of protein folding, binding, and aggregation

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