Form Follows Sequence

Nevertheless, while improvements in the underlying model are needed, global-optimization results have been sufficiently encouraging to attempt larger proteins with more complex structures, including pure beta sheets and mixed alpha-helix, beta-sheet proteins.

Bundles and Beads and Barrels and Saddles

Proteins are like strings of beads wound into bundles. Their structure is described at increasingly intricate levels. Primary structure is a chain of amino-acid residues, chemical units linked to their neighbors by peptide bonds, like snap-together plastic beads. The 20 amino acids that can form proteins differ in size, shape, electric charge and polarity (which affects interaction with water), hydrophobicity ("oiliness"), and other properties. Researchers have assigned single-letter designations to each, from A for alanine through Y for tyrosine; thus primary structure, the polypeptide chain, is given by a string of letters, e.g., MEIMKKQNSQINEINKDEIFV. . . .

Secondary structure results from the angles between amino acids, plus the hydrogen bonds that may form from one residue to another. Repeating bonds and angles commonly form alpha helices and beta sheets (or sometimes variations of these) and their hairpin or crossover connections-plus a variety of turns, which often expose active chemical groups on the protein surface, and a few other structures such as loops and "paperclips."

Tertiary structures are made from helices, sheets, and other secondary elements. A particular configuration of these is called a fold. There are roughly 500 known folds, a dozen of which occur very commonly, some with names like "barrel" or "sandwich" or "saddle"-out of some 6,000 to 10,000 predicted to exist. Remarkably, many proteins that have completely different sequences of amino acids are structurally identical-a strong hint that this structure has inherent evolutionary advantage.

While a protein may consist of a single polypeptide strand incorporating a particular fold, others are built from separate strands. A famous example of quaternary structure is hemoglobin, which combines two pairs of identically folded chains in a single molecule capable of snapping up, carrying, and releasing oxygen in the bloodstream and tissues of the human body.

In vivo, In vitro, In silico