Amino Acids and Protein Architecture

Proteins are polymers built from 20 different monomers called amino acids. Every amino acid shares a common backbone: a central **$\alpha$-carbon bonded to an amino group** ($-NH_2$), a carboxyl group ($-COOH$), and a hydrogen atom. The fourth bond is occupied by a variable R-group (side chain). This R-group is the 'identity' of the amino acid. Based on the R-group's structure, amino acids are classified as non-polar (hydrophobic), polar (hydrophilic), acidic (negatively charged), or basic (positively charged). In the cellular environment ($pH \approx 7.4$), amino acids exist as zwitterions, where the amino group is $-NH_3^+$ and the carboxyl group is $-COO^-$.

To form a protein, amino acids link together via a condensation reaction (dehydration synthesis). The carboxyl group of one amino acid reacts with the amino group of another, releasing a molecule of $H_2O$. The resulting covalent bond is called a peptide bond—specifically, it is an amide linkage. This process creates a repeating sequence of $N-C_{\alpha}-C$ atoms known as the polypeptide backbone. Because one end of the chain has a free amino group (N-terminus) and the other has a free carboxyl group (C-terminus), polypeptides have a specific directionality.

Protein folding occurs in four distinct stages. Primary structure is simply the linear sequence of amino acids. Secondary structure involves local folding into **$\alpha$-helices or $\beta$-pleated sheets, stabilized by hydrogen bonds** between the $C=O$ and $N-H$ groups of the backbone. Tertiary structure is the overall 3D shape of a single polypeptide, driven by R-group interactions (hydrophobic collapse, ionic bonds, and disulfide bridges). Finally, Quaternary structure occurs when multiple polypeptide chains (subunits) assemble into a single functional unit, such as hemoglobin.