We have recently developed a novel quantum chemical approach, referred to as QM/MM-ER, to compute quantum chemically the solvation free energy of a molecule in a solution. The point of our method is to combine the hybrid QM/MM (quantum mechanical/molecular mechanical) approach with a novel statistical theory of solutions termed as theory of energy representation. Within the framework of the QM/MM-ER approach, the solvation free energy of a solute is constructed in terms of the distribution functions between the solute and the solvent for the solution and the pure solvent systems. In this paper, we extend our method to a biological molecule with structural flexibility. The pilot system we choose is a small peptide chain Chignolin consisting of 10 amino acid residues immersed in water. The solvation free energy of the peptide chain has been evaluated as -230.8kcal/mol by QM/MM-ER. However, the energy distribution function for a solution system has non-zero values on such the lower energy coordinate that the distribution for the pure solvent completely vanishes, which gives rise to a loss of accuracy in the free energy calculation. We discuss the origin for such the unfavorable situation as well as the method to conquer the problem.