Figure 1.

Illustrations of the protein energy landscape for different models. For illustrative purposes, the coordinates q₁ and q₂ schematically present the protein conformational space, which has, in reality, hundreds of dimensions. (a) The energy landscape for the “golf course” model. (b) A general “energy funnel” illustration. The funnel centers on the protein native structure having the lowest energy. (We should remind that the term "entropy" in the context of protein folding models conventionally refers only to the configurational entropy, while the term "energy" refers to the free energy of interactions, so that solvent-mediated forces (for example, hydrophobic and electrostatic ones), with all their solvent entropy [40] come within "energy"; therefore, we avoid applying the word “enthalpy” to protein folding models.) (c) A more detailed general energy landscape. The term “gap” denotes an energy gap between the global and other energy minima, necessary to provide the “all-or-none” transition between native and other structures of the chain. The gap must be large enough, of many k_BT_melt, where T_melt is protein melting temperature (thus, usually, k_BT_melt ≈ 0.7 kcal/mol). Adapted from [46] with some modifications.