Thermodynamic Folding-Unfolding Transition and Potential Energy Landscape of a Mini-Protein Chignolin

In this study, multicanonical generalized hybrid Monte Carlo calculations have been performed for the hydrated chignolin using a generalized Born=surface area implicit solvent model. An order-disorder transition regarding the chignolin has been detected by monitoring the heat capacity. The low-temperature ordered phase is well characterized by the experimentally observed native state, and the high-temperature phase is dominated by denatured structures. Inherent structure analysis has been performed to describe the energy landscape of the chignolin. The lowest energy inherent structure group corresponds to the native structure of the chignolin. Other inherent structure groups include the wellknown misfolded structure and the intermediate structure found in previous studies. For representative structures of the inherent structure groups, three-dimensional reference interaction site model integral equation theory calculations have been performed to gain information on the improvability of the deficiency by the implicit solvent model.