One computational approach being developed is to describe a 3D structure by a 3D profile. The 3D profile can score the compatibility of any amino acid sequence with the 3D structure. A high compatibility score indicates the sequence may be folded as the structure. A second approach is to test rules of protein folding by designing and synthesizing a simple protein, and then using x-ray crystallography to compare the actual structure with the design. These are semi-empirical quantities that characterize interactions of amino acid residues.
ASPs give an estimate of the hydrophobic contribution to the free energy of interaction.