New insights into the multiple minima problem associated with the conformational space of peptides

The distribution of minima of thorough conformational searches of the pentapeptide met-enkephalin and the nonapeptide bradykinin was compared with the density of states of a flexible molecule described using the rotational isomeric approximation. It is observed that minima distributions generated from the conformational search and the density of states of the rotational isomeric model exhibit the same feature: an asymmetric distribution with a maximum. This result together with the energy landscape of a polypeptide provides new insights into the multiple minima problem. The implications on devising more robust conformational search strategies are discussed.