What is a Macromolecule?

Macromolecules refer to biological substances with a relative molecular mass of more than 5000, or even more than one million, such as proteins, nucleic acids, polysaccharides, and the like. It is closely related to life activities and consists of simple molecular units that are considered monomers. There is a substance that forms a gel in the solution. Generally, compounds with a relative molecular mass exceeding 10,000 are called macromolecular compounds or high molecular compounds. It is composed of many repeating structural units, and generally has a linear structure, and some have a dendritic structure. Many substances with important biological functions, such as proteins and nucleic acids, belong to this class of compounds. The basic constituent unit or building-block molecule of a macromolecular protein is amino acid (AA).

Macromolecule

Macromolecule means relative

Discover the background of macromolecules

In 1912, German physicist M.von Laue predicted that crystals were natural diffraction gratings for X-rays. Later British physicists WH Bouguer and WL Bouguer pioneered X-ray crystallography. For decades, this discipline has continued to evolve and improve, determining the crystal and molecular structures of thousands of inorganic and organic compounds. The structural information provided by it has become the basis of modern structural chemistry. However, the traditional method for analyzing the crystal structure of small molecules is not suitable for biological macromolecules with many atoms and complex structures. It was not until 1954 that British crystallographers and others proposed an isomorphous substitution method that introduced heavy atoms in protein crystals, and it was then possible to determine the crystal structure of biological macromolecules. In 1960, British crystallographer JC Kendrew and others first solved the three-dimensional structure of a protein molecule consisting of 153 amino acids and a molecular weight of 17,500, myoglobin. Figure 1 [Structural model of the myoglobin molecule of the giant whale] shows a structural model with a resolution of 2 angstroms. Since then, research work on the crystal structure of biological macromolecules has developed rapidly. By the early 1980s, the three-dimensional structures of nearly 200, and other biological macromolecules had been determined, which has strongly promoted the development of molecular biology. Following the first artificial synthesis of bovine insulin in China in the 1960s, the three-dimensional structure of tripartite dizinc pig insulin was determined in the early 1970s. In 1986, China has completed the 1.2 Angstrom high-resolution correction of this structure.

Crystal and X-ray diffraction

Electromagnetic waves propagate in a straight line, but in some cases they also turn. This is the phenomenon of diffraction. This phenomenon occurs when visible light passes through a pinhole or slit. Because the size of the pinhole or slit is the same as the wavelength of visible light, the pinhole or slit can be regarded as a point light source, which emits secondary electromagnetic waves, or scattered waves, in all directions. If there are multiple pinholes or slits arranged in order, due to the interference of these scattered waves, a regular light and dark diffraction pattern will be formed. This is because the scattered waves from different parts have different phases and amplitudes. The result of their addition is strengthened in some places and weakened in others. These patterns vary with the wavelength or the size of the pinholes and their arrangement (Figure 2 [Three pinhole arrangements and their corresponding diffraction patterns]). When X-rays pass through the crystal, the extranuclear electrons of the atoms in the crystal can scatter X-rays. If each atom is regarded as a scattering source, since the wavelength of X-rays is the same as the distance between the atoms, diffraction will also occur. The crystal structure is characterized by the periodic arrangement of atoms or molecules within the crystal. If a set of abstract geometric points is used to represent this periodic repeating rule, this arrangement can be expressed as a lattice. The three-dimensional lattice structure of the crystal allows the crystal to be divided into numerous parallelepipeds of exactly the same size and shape, which are called unit cells. It is the basic repeating unit of crystal structure. Each unit cell contains atoms of the same type, number, and arrangement. It can be concluded that the intensity of the diffraction line (also called the reflection line) depends on the content of the unit cell, and its direction depends on the wavelength and the size and shape of the unit cell.

Crystal structure determination

The diffraction of X-rays, neutron beams and electron beams by crystals follows the same optical transformation principle as the diffraction of visible light by regularly arranged pinholes. The Fourier transform can obtain their reciprocal images-diffraction spectra. Conversely, the inverse transformation of the diffraction spectrum is an image in positive space-the arrangement of pinholes or the structure of a crystal. In visible light diffraction, this inverse transformation can be achieved by the focusing process of the lens. But so far, no way has been found to focus X-ray (or neutron) scattered rays. Therefore, it is impossible to directly observe the image of biological macromolecules. This can only be done mathematically with the aid of an electronic computer.