While the mechanisms of protein folding and predictability from primary structure are still mysterious, nature has afforded us a few clues from which to work. There are over 400 protein structures known by X-ray diffraction. From solution and solid state morphology and denaturation studies, we know proteins pay a high price for charge burial. Reverse turns, hairpins and loops are places about which polypeptide structures separate domains in proteins. Increased frequency of hydrophobic residues about b -sheets implies that sheets have hydrophobic faces.
Helices can pack with enough energy to drive dimerization.
Furthermore, domains excised from native conformations of proteins that are spatially related, often tend to dimerize in solution. These phenomena imply a relationship between the nature of hydrophobic cores of protein interiors and heterodimerization. Thus, design of hydrophobic cores reduces to one of molecular recognition, a central problem in many subdisciplines of chemistry. Our approach includes the design of prosthetic units linked to peptide chains that include the above factors. Water Soluble Organic Molecules for the Molecular Recognition of Oxo-anions Water is the most competitive solvent in its solvation of anions.