Structural biology is a field that is many centuries old which, as defined by the Journal of Structural Biology, deals with structural analysis of living material at every level of organization. Early structural biologists throughout the 19th and early 20th centuries were primarily only able to study structures to the limit of the naked eye's visual acuity and through magnifying glasses and light microscopes.
The Protein Data Bank (PDB) is a database for the three-dimensional structural data of large biological molecules, such as proteins and nucleic acids. The data, typically obtained by X-ray crystallography, NMR spectroscopy, or, increasingly, cryo-electron microscopy, and submitted by biologists and biochemists from around the world, are freely accessible on the Internet via the websites of its member organisations. The PDB is overseen by an organization called the Worldwide Protein Data Bank, wwPDB.
Structural bioinformatics is the branch of bioinformatics that is related to the analysis and prediction of the three-dimensional structure of biological macromolecules such as proteins, RNA, and DNA. It deals with generalizations about macromolecular 3D structures such as comparisons of overall folds and local motifs, principles of molecular folding, evolution, binding interactions, and structure/function relationships, working both from experimentally solved structures and from computational models. The term structural has the same meaning as in structural biology, and structural bioinformatics can be seen as a part of computational structural biology. The main objective of structural bioinformatics is the creation of new methods of analysing and manipulating biological macromolecular data in order to solve problems in biology and generate new knowledge.
Transmission electron cryomicroscopy (CryoTEM), commonly known as cryo-EM, is a form of cryogenic electron microscopy, more specifically a type of transmission electron microscopy (TEM) where the sample is studied at cryogenic temperatures. Cryo-EM, specifically 3-dimensional electron microscopy (3DEM), is gaining popularity in structural biology.
Cryo-electron tomography (cryo-ET) is an imaging technique used to produce high-resolution (~1–4 nm) three-dimensional views of samples, often biological macromolecules and cells. cryo-ET is a specialized application of transmission electron cryomicroscopy (CryoTEM) in which samples are imaged as they are tilted, resulting in a series of 2D images that can be combined to produce a 3D reconstruction, similar to a CT scan of the human body. In contrast to other electron tomography techniques, samples are imaged under cryogenic conditions. For cellular material, the structure is immobilized in non-crystalline, vitreous ice, allowing them to be imaged without dehydration or chemical fixation, which would otherwise disrupt or distort biological structures.
MRC is a file format that has become an industry standard in cryo-electron microscopy (cryoEM) and electron tomography (ET), where the result of the technique is a three-dimensional grid of voxels each with a value corresponding to electron density or electric potential. It was developed by the MRC Laboratory of Molecular Biology. In 2014, the format was standardised. The format specification is available on the CCP-EM website.
The Worldwide Protein Data Bank, wwPDB, is an organization that maintains the archive of macromolecular structure. Its mission is to maintain a single Protein Data Bank Archive of macromolecular structural data that is freely and publicly available to the global community.
In X-ray crystallography, a difference density map or Fo–Fc map shows the spatial distribution of the difference between the measured electron density of the crystal and the electron density explained by the current model.
Helen Miriam Berman is a Board of Governors Professor of Chemistry and Chemical Biology at Rutgers University and a former director of the RCSB Protein Data Bank. A structural biologist, her work includes structural analysis of protein-nucleic acid complexes, and the role of water in molecular interactions. She is also the founder and director of the Nucleic Acid Database, and led the Protein Structure Initiative Structural Genomics Knowledgebase.
Resolution in terms of electron density is a measure of the resolvability in the electron density map of a molecule. In X-ray crystallography, resolution is the highest resolvable peak in the diffraction pattern, while resolution in cryo-electron microscopy is a frequency space comparison of two halves of the data, which strives to correlate with the X-ray definition.
In structural biology, as well as in virtually all sciences that produce three-dimensional data, the Fourier shell correlation (FSC) measures the normalised cross-correlation coefficient between two 3-dimensional volumes over corresponding shells in Fourier space (i.e., as a function of spatial frequency). The FSC is the three-dimensional extension of the two-dimensional Fourier ring correlation (FRC); also known as: spatial frequency correlation function.
Biology data visualization is a branch of bioinformatics concerned with the application of computer graphics, scientific visualization, and information visualization to different areas of the life sciences. This includes visualization of sequences, genomes, alignments, phylogenies, macromolecular structures, systems biology, microscopy, and magnetic resonance imaging data. Software tools used for visualizing biological data range from simple, standalone programs to complex, integrated systems.
Single particle analysis is a group of related computerized image processing techniques used to analyze images from transmission electron microscopy (TEM). These methods were developed to improve and extend the information obtainable from TEM images of particulate samples, typically proteins or other large biological entities such as viruses. Individual images of stained or unstained particles are very noisy, and so hard to interpret. Combining several digitized images of similar particles together gives an image with stronger and more easily interpretable features. An extension of this technique uses single particle methods to build up a three-dimensional reconstruction of the particle. Using cryo-electron microscopy it has become possible to generate reconstructions with sub-nanometer resolution and near-atomic resolution first in the case of highly symmetric viruses, and now in smaller, asymmetric proteins as well. Single particle analysis can also be performed by induced coupled plasma mass spectroscopy (ICP-MS).
David S. Goodsell, is an associate professor at the Scripps Research Institute and research professor at Rutgers University, New Jersey. He is especially known for his watercolor paintings of cell interiors.
The term macromolecular assembly (MA) refers to massive chemical structures such as viruses and non-biologic nanoparticles, cellular organelles and membranes and ribosomes, etc. that are complex mixtures of polypeptide, polynucleotide, polysaccharide or other polymeric macromolecules. They are generally of more than one of these types, and the mixtures are defined spatially, and with regard to their underlying chemical composition and structure. Macromolecules are found in living and nonliving things, and are composed of many hundreds or thousands of atoms held together by covalent bonds; they are often characterized by repeating units. Assemblies of these can likewise be biologic or non-biologic, though the MA term is more commonly applied in biology, and the term supramolecular assembly is more often applied in non-biologic contexts. MAs of macromolecules are held in their defined forms by non-covalent intermolecular interactions, and can be in either non-repeating structures, or in repeating linear, circular, spiral, or other patterns. The process by which MAs are formed has been termed molecular self-assembly, a term especially applied in non-biologic contexts. A wide variety of physical/biophysical, chemical/biochemical, and computational methods exist for the study of MA; given the scale of MAs, efforts to elaborate their composition and structure and discern mechanisms underlying their functions are at the forefront of modern structure science.
Macromolecular structure validation is the process of evaluating reliability for 3-dimensional atomic models of large biological molecules such as proteins and nucleic acids. These models, which provide 3D coordinates for each atom in the molecule, come from structural biology experiments such as x-ray crystallography or nuclear magnetic resonance (NMR). The validation has three aspects: 1) checking on the validity of the thousands to millions of measurements in the experiment; 2) checking how consistent the atomic model is with those experimental data; and 3) checking consistency of the model with known physical and chemical properties.
Cryogenic electron microscopy (cryo-EM) is a cryomicroscopy technique applied on samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of vitreous ice. An aqueous sample solution is applied to a grid-mesh and plunge-frozen in liquid ethane or a mixture of liquid ethane and propane. While development of the technique began in the 1970s, recent advances in detector technology and software algorithms have allowed for the determination of biomolecular structures at near-atomic resolution. This has attracted wide attention to the approach as an alternative to X-ray crystallography or NMR spectroscopy for macromolecular structure determination without the need for crystallization.
Sjors Hendrik Willem ScheresFRS is a Dutch scientist at the MRC Laboratory of Molecular Biology Cambridge, UK.
Bridget Olivia Carragher is a South African physicist specialized in electron microscopy.
Microcrystal electron diffraction, or MicroED, is a CryoEM method that was developed by the Gonen laboratory in late 2013 at the Janelia Research Campus of the Howard Hughes Medical Institute. MicroED is a form of electron crystallography where thin 3D crystals are used for structure determination by electron diffraction. Prior to this demonstration, macromolecular (protein) electron crystallography was only used on 2D crystals, for example.
