Thermodynamic cycle for calculating the contribution of a side-chain to the protein folding free energy. ΔGfoldingis the folding free energy of the protein in the presence of all amino acids including the one at position i. (BB) is the folding free energy of the protein in the absence of the side chain at position i. ΔGw-solv(SC) is the free energy cost of introducing the side chain of residue i into the water solvent. ΔG
(SC) is the free energy cost of introducing the same side chain into the folded protein structure. ΔG
(SC) includes the energy of interaction of the side chain with the surrounding residues in the protein structure, as well as the cost of burying the atoms of both the side chain and the surrounding protein structure.