Energetics was analyzed for cytochrome c in pure-water solvent and in a urea-water mixed solvent to elucidate the solvation effect in the structural variation of the protein. The solvation free energy was computed through all-atom molecular dynamics simulation combined with the solution theory in the energy representation, and its correlations were examined over sets of proteinstructures against the electrostatic and van der Waals components in the average interactionenergy of the protein with the solvent and the excluded-volume component in the solvation free energy. It was observed in pure-water solvent that the solvation free energy varies in parallel to the electrostatic component with minor roles played by the van der Waals and excluded-volume components. The effect of urea on proteinstructure was then investigated in terms of the free-energy change upon transfer of the proteinsolute from pure-water solvent to the urea-water mixed solvent. The decomposition of the transfer free energy into the contributions from urea and water showed that the urea contribution is partially canceled by the water contribution and governs the total free energy of transfer. When correlated against the change in the solute-solvent interactionenergy upon transfer and the corresponding changes in the electrostatic, van der Waals, and excluded-volume components, the transfer free energy exhibited strong correlations with the total change in the solute-solvent energy and its van der Waals component. The solute-solvent energy was decomposed into the contributions from the protein backbone and side chain, furthermore, and neither of the contributions was seen to be decisive in the correlation to the transfer free energy.