Minimal model for studying prion‐like folding pathways

Abstract

The Monte Carlo technique is used to simulate the energy landscape and the folding kinetics of a minimal prion-like protein model. We show that the competition between hydrogen-bonding and hydrophobic interactions yields two energetically favored secondary structures, an alpha-helix and a beta-hairpin. Folding simulations indicate that the probability of reaching the alpha-helix form from a denatured random conformation is much higher than the probability of reaching the beta-sheet form, even though the beta-sheet has a lower energy. The existence of a lower energy beta-sheet state gives the possibility for the normal alpha-helix structure to take a structural transformation into the beta-sheet structure under external influences.