1. Liquid water molecules, at life-supporting temperatures, form groups (lattices) that are hydrogen-bonded networks ({H₂O}_20-30). Thermodynamic considerations tell us that the formation of these lattices arise as H₂O molecules attempt to optimize the number of energetically favorable H-bonds. Consider what happens, then, if hydrophobic, amino acid sidechains "poke" into the aqueous solvent. When this situation arises, shown above for two phenylalanine residues, the H₂O lattice is disrupted and H₂O molecules form a shell around the non-polar sidechains with which they cannot chemically interact. These H₂O's are unable to participate in H-bonding and lose freedom of movement, both of which are energetically unfavorable events.

2. However, if the hydrophobic molecules are closely juxtaposed, shown above for the two phenylalanine sidechains, some H₂O molecules are "freed", allowing their participation in lattice formation. This is quite energetically favorable, and results in maximal association of hydrophobic molecules in an aqueous solvent, i.e. hydrophobic bond formation. The energetics of hydrophobic bond formation drives amino acids with hydrophobic sidechains into the interior of proteins, in most cases; this is a very important component of proper protein folding.