Structural computational biology: introduction and background  (Page 2/6)

The primary structure of a protein is easily obtainable from its corresponding gene sequence, as well as by experimental manipulation. Unfortunately, the primary structure is only indirectly related to the protein's function. In order to work properly, a protein must fold to form a specific three-dimensional shape, called its native structure or native conformation . The three-dimensional structure of a protein is usually understood in a hierarchical manner. Secondary structure refers to folding in a small part of the protein that forms a characteristic shape. The most common secondary structure elements are α-helices and β-sheets , one or both of which are present in almost all natural proteins.

Experimental methods for protein structure determination

A structure of a protein is a three-dimensional arrangement of the atoms such that the integrity of the molecule (its connectivity) is maintained. The goal of a protein structure determination experiment is to find a set of three-dimensional (x, y, z) coordinates for each atom of the molecule in some natural state. Of particular interest is the native structure, that is, the structure assumed by the protein under its biological conditions, as well as structures assumed by the protein when in the process of interacting with other molecules. Brief sketches of the major structure determination methods follow:

X-ray crystallography

The most commonly used and usually highest-resolution method of structure determination is x-ray crystallography . To obtain structures by this method, laboratory biochemists obtain a very pure, crystalline sample of a protein. X-rays are then passed through the sample, in which they are diffracted by the electrons of each atom of the protein. The diffraction pattern is recorded, and can be used to reconstruct the three-dimensional pattern of electron density, and therefore, within some error, the location of each atom. A high-resolution crystal structure has a resolution on the order of 1 to 2 Angstroms (Å). One Angstrom is the diameter of a hydrogen atom (10^-10 meter, or one hundred-millionth of a centimeter).