A theoretical analysis on hydration thermodynamics of proteins.

The hydration free energy (HFE) of several proteins modeled using the all-atom force field is calculated by employing the three-dimensional reference interaction site model theory, a recently developed integral equation theory of molecular solvation. The HFE is decomposed into the energetic and entropic components under the isochoric condition. The former comprises the protein-water interaction energy and the water reorganization energy arising from the structural changes induced in water. Each component is further decomposed into the nonelectrostatic and electrostatic contributions. It is found that the HFE is governed by the nonelectrostatic hydration entropy and the electrostatic hydration energy. The nonelectrostatic hydration entropy is almost exclusively ascribed to the translational entropy loss of water upon the protein insertion. It asymptotically becomes proportional to the excluded volume (EV) for water molecules as the protein size increases. The hydration energy is determined by the protein-water interaction energy which is half compensated by the water reorganization energy. These energy terms are approximately proportional to the water-accessible surface area (ASA). The energetic and entropic contributions are balanced with each other and the HFE has no apparent linear relation with the EV and ASA.