Importance of Metastable States in the Free Energy Landscapes of Polypeptide Chains

We show that the interplay between excluded vol. effects, hydrophobicity, and hydrogen bonding in a tubelike representation of a polypeptide chain gives rise to free energy landscapes that in addn. to a clear global min., are characterized by the general presence of a small no. of metastable min., which correspond to common structural motifs obsd. in proteins. The complexity of the landscape increases only moderately with the length of the chain. Anal. of the temp. dependence of these landscapes reveals that the stability of specific metastable states is maximal at a temp. close to the midpoint of folding. These metastable states are therefore likely to be of particular significance in detg. the generic tendency of proteins to aggregate into potentially pathogenic agents.