Minimal model for studying prion‐like folding pathways

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 α‐helix and a β‐hairpin. Folding simulations indicate that the probability of reaching the α‐helix form from a denatured random conformation is much higher than the probability of reaching the β‐sheet form, even though the β‐sheet has a lower energy. The existence of a lower energy β‐sheet state gives the possibility for the normal α‐helix structure to take a structural transformation into the β‐sheet structure under external influences. Proteins 2003;51:283–288. © 2003 Wiley‐Liss, Inc.