The Native Energy Landscape for Interleukin-1β. Modulation of the Population Ensemble through Native-state Topology

A minimalist Gō-model, with no energetic frustration in the native conformation, has been shown to describe accurately the folding pathway of the β-trefoil protein, interleukin-1β (IL-1β). While it appears that these models successfully model transition states and intermediates between the unfolded and native ensembles, it is unclear how accurately they capture smaller, yet biologically relevant, structural changes within the native ensemble after energetic perturbation. Here, we address the following questions. Can a simple Gō-model of interleukin-1β, based on native topology, describe changes in structural properties of the native ensemble as the protein stability is changed? Or is it necessary to include a more explicit representation of atoms, electrostatic, hydrogen bonding, and van der Waals forces to describe these changes?