Folding a protein with equal probability of being helix or hairpin.

We explore the possibility for the native structure of a protein being inherently multiconformational in an ab initio coarse-grained model. Based on the Wang-Landau algorithm, the complete free energy landscape for the designed sequence 2DX4: INYWLAHAKAGYIVHWTA is constructed. It is shown that 2DX4 possesses two nearly degenerate native structures: one is a helix structure with the other a hairpinlike structure, and their free energy difference is <2% of that of local minima. Two degenerate native structures are stabilized by an energy barrier of ∼10 kcal/mol. Furthermore, the hydrogen-bond and dipole-dipole interactions are found to be two major competing interactions in transforming one conformation into the other. Our results indicate that two degenerate native structures are stabilized by subtle balance between different interactions in proteins. In particular, for small proteins, balance between the hydrogen-bond and dipole-dipole interactions happens for proteins of sizes being ∼18 amino acids and is shown to the main driving mechanism for the occurrence of degeneracy. These results provide important clues to the study of native structures of proteins.