Free-energy analysis of protein solvation with all-atom molecular dynamics simulation combined with a theory of solutions

•Endpoint method for computing the solvation free energy of protein.•Compensation of the intramolecular and hydration effects in equilibrium fluctuation of protein structure.•Correlation analyses for energetics of hydration and cosolvent effects.•Role of solvent water in protein-protein docking structure determination.

The structure of a protein is strongly influenced by solvation. In the present review, the solvation effect is treated within the framework of statistical thermodynamics. The key quantity is the solvation free energy of protein and a fast method for its computation with explicit solvent is introduced. The applications of the method to the structural fluctuation of protein in water, structure determination of protein-protein complex, and urea effect on protein structure are then described, and the roles of solvent water and cosolvent are discussed from the standpoint of energetics.

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