The Effect of Nonnative Interactions on the Energy Landscapes of Frustrated Model Proteins

Abstract EN

The 46- and 69-residue BLN model proteins both exhibit frustrated folding to β-barrel structures.

We study the effect of varying the strength of nonnative interactions on the corresponding energy landscapes by introducing a parameter λ, which scales the potential between the BLN (λ=1) and Gō-like (λ=0) limits.

We study the effect of varying λ on the efficiency of global optimisation using basin-hopping and genetic algorithms.

We also construct disconnectivity graphs for these proteins at selected values of λ.

Both methods indicate that the potential energy surface is frustrated for the original BLN potential but rapidly becomes less frustrated as λ decreases.

For values of λ≤0.9, the energy landscape is funnelled.

The fastest mean first encounter time for the global minimum does not correspond to the Gō model: instead, we observe a minimum when the favourable nonnative interactions are still present to a small degree.