Globally the energy landscape of a folding protein resembles a partially rough funnel. The local roughness of the funnel reflects transient trapping of the protein configurations in local free energy minima.
A consequence of minimizing energetic frustration is that the topology of the native fold also plays a major role in the folding mechanism. Some folding motifs are easier to design than others suggesting the possibility that evolution not only selected sequences with sufficiently small energetic frustration but also selected more easily designable native structures. The overall structure of the on-route and off-route (traps) intermediates for the folding of more complex proteins is also strongly influenced by topology.
Many cellular functions rely on interactions among proteins and between proteins and nucleic acids. The limited success of binding predictions may suggest that the physical and chemical principles of protein binding have to be revisited to correctly capture the essence of protein recognition. Going beyond folding, the power of reduced models to study the physics of protein assembly will be discussed. Since energetic frustration is sufficiently small, native topology-based models, which correspond to perfectly unfrustrated energy landscapes, have shown that binding mechanisms are robust and governed primarily by the protein's native topology. These models impressively capture many of the binding characteristics found in experiments and highlight the fundamental role of flexibility in binding. Deciphering and quantifying the key ingredients for biological self-assembly is invaluable to reading out genomic sequences and understanding cellular interaction networks. Going even beyond binding, we will be discussing the energy landscape for the molecular motor kinesin.
Coffee and cookies before the presentation at 1:00 pm, and refreshments after the presentation will both be served in Room 128.