Hydrophobic Interaction Chromatography: Hydrophobic interaction chromatography exploits the ability of  a strong interaction between hydrophobic group attached to the matrix and hydrophobic patches present on an analyte such as protein. Protein is made-up of amino acids with acidic, basic, polar and non-polar (aliphatic or aromatic) side chain. Protein is synthesized from ribosome as a linear chain and afterwards it gets folded into a 3-D conformation mostly guided by the environment of side chain and the outer medium. Local environment in a cell is aqeous and it favors the folding of protein to keep the polar or charged amino acids on the surface and non-polar side chain within the inner core (Figure 31.1). Most of the hydrophobic amino acids are shielded from the outer polar environment where as polar amino acid present on the surface has bound water molecule to form a hydration shell. 

Figure 31.1: Folding of Protein in an aqueous environment. Following a series of folding stages, protein adopts a 3-D conformation with hydrophobic patches present in the core.