All-Atom Analysis of Free Energy of Protein Solvation Through Molecular Simulation and Solution Theory
Solvation affects the protein structure strongly, and its effect is quantified by the solvation free energy in statistical thermodynamics. In the present chapter, a fast and accurate method of computation is introduced for the free energy of protein solvation with explicit solvent. The application of the method is then presented for the equilibrium fluctuation in pure-water solvent and the effect of urea on the protein structure. The roles of the solvent water and the urea cosolvent are discussed from the standpoint of energetics, and it is seen that the variation of the protein structural energy is induced and compensated by the solvent water during the course of equilibrium fluctuation. The unfolding mechanism of added urea is also addressed in terms of the energetics of transfer of the protein solute from pure-water solvent to the urea–water mixed solvent, and an extended structure of protein is shown to be favored through the direct, van der Waals interaction between the protein and urea.
KeywordsSolvation Free energy Solution theory Molecular dynamics simulation Cosolvent
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