FIGURE 1.

Thermodynamic cycle for calculating the contribution of an amino acid side chain to the folding free energy of a decoy structure. ΔG folding is the contribution of the considered residue (back bone and side chain) to the free energy of folding of the protein (here the decoy). ΔG (BB) folding is the contribution of the backbone of the considered residue to the folding free energy of the decoy. Δ_Gw-solv(SC) is the free energy cost of introducing the side chain into the water solvent. ΔG_d-solv (SC), is the free energy cost of introducing the same side chain into the decoy structure. This cost includes the interaction energy of the side chain with the surrounding residues in the decoy as well as the cost of burying side-chain atoms and surrounding decoy atoms.