Figure 21.

Frustration can affect proteins’ internal friction. Search in a rough energy landscape is affected by the population of local traps. When there are many traps these can be thought of as a source of friction on the diffusive folding. The structurally similar Spectrin repeats were shown to fold with very different rates (Wensley et al. 2010). The frustratograms of a natural protein that include these repeats is shown. R16 and R17 have a central cluster of highly frustrated residues and fold three orders of magnitude slower than does R15, which is more uniformly minimally frustrated. This central cluster of frustrated residues is involved in the main crossing from an initial transition state for folding to a later exit transition state for folding (Borgia et al. 2012). The frictional effect can be revealed by the viscosity dependence of the folding reactions, which can be studied by varying the solvent conditions and keeping the relative stabilities unchanged. For R15 the folding rate scales inversely to the solvent viscosity while for the frustrated systems R16 and R17 the folding rates are independent of solvent viscosity (Wensley et al. 2010).