The physical and chemical properties of the R-groups dominate the primary physical and chemical differences between AAs.  Likewise, R-group differences also dominate the physical and chemical contribution each AA residue makes to the inherent properties of a polypeptide or protein. Therefore, it is useful to review the fundamental physical or chemical properties of the R-groups themselves.

Note that the larger R-groups in this class of AAs tend to be highly nonpoloar, hydrophobic ("water fearing") in character. In other words, the R-groups of the larger AAs (i.e., those AAs excluding Ala , Gly and Pro) tend to be repelled by water and thus tend to be thermodynamically sequestered into "oily" clusters in aqueous solutions. These R-groups are typically abundant in the core of folded protein in aqueous solution, giving the protein an oil-droplet-like center shielded from contact with water molecules in the immediate environment. It is important to note, however, that these R-groups can also exist in contact with water and most folded proteins will have a certain percentage of its AA residues with nonpolar R-groups in direct contact with the aqueous environment. Typically, a relatively delicate thermodynamic balance exists between the numbers of nonpolar R-groups of a protein that are in contact the aqueous environment as opposed to those that exist in the hydrophobic core of a protein. The delicacy of this balance is revealed by the fact that relatively mild perturbations in the environment of a protein - e.g., changes in temperature, pH, ionic strength, electrolyte concentrations or composition, etc. -- often leads to sharp transitions in the structure of a protein and loss of biological activity, referred to as "denaturation."

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