Relationship between protein folding thermodynamics and the energy landscape.

The origin of protein folding thermodynamics is examined in terms of the energy landscape, employing an off-lattice protein model with scaled non-native attractions, which is continuously tunable between a Go-like model and a highly frustrated system. Extensive statistical temperature molecular dynamics simulations, combined with inherent structure analysis, reveal the intimate connection between the global geometric properties of the energy landscape and the statistical temperature. The basin depth of the energy landscape is shown to play a key role in the first-order-like characteristics of the statistical temperature, which are easily identified by the squared modulus of the potential energy gradient in the microcanonical ensemble.