Seeing the Invisible: 50 Years of Macromolecular Visualization



A very large molecule formed of (covalently) bonded, smaller, repeating units.
Protein, RNA, and DNA
Different types of linear macromolecules found in cells. All three take up structures--proteins are said to fold--that are key to their biological function.
Atomic model
The physical or computer representation of the three-dimensional position of the atoms in a molecule.
Protein backbone vs sidechains
The linearly connected part of protein vs the short dangling chains off of that backbone.
Cα, or alpha-carbon
In each repeating unit of the protein backbone, the Cα is the atom from which the sidechain branches off. The backbone atoms between one Cα and the next all lie in a plane, called a peptide.
α-helix, β-sheet
Common local substructures in protein backbone, where each unit's conformation is the same.
Monomer, dimer, etc
Having just one, or several, copies of a molecule in the functional unit, such as the two-chain functional dimer of SOD or the cooperative tetramer of hemoglobin that binds oxygen.
Worm drawing
An intermediate form in developing ribbon drawings.
X-ray diffraction
The scattering of X-rays off of the electrons in matter. From the repeating lattice of a crystal, that process gives localized diffraction spots.
X-ray crystallography
The use of X-ray diffraction to determine the three-dimensional structure of matter. Because a high density of electrons denotes the presence of an atom, this information can be used to reconstruct atomic positions.
Fourier transform
The mathematical operation used to transform back and forth between the measured intensities of the X-ray diffraction spots and the electron density in a crystal. That calculation does for X-rays what a physical lens does to form an image with visible light.
Electron density
It is the electrons around each atom that scatter X-rays, so what they image is the density of electrons at each position in the molecule; the electrons are densest around atoms, so at high resolution they show a peak for each atom.
The spatial precision to which electron density, and thus atoms, can be located. It depends on how many diffraction spots can be detected, which in turn depends on how similar all copies of the molecule are within the crystal. The higher the resolution, the lower the number in Å.
10-10 meters, about one million times smaller than the thickness of a human hair.
Cryogenic electron microscopy. An electron microscopy (EM) technique recently revolutionized to enable structure determination of biological macromolecules at better than 4Å resolution. It combines thousands of low-dose, two-dimensional images into a "three-dimensional image reconstruction" that looks a great deal like an electron density map.