Proteins are the molecular workhorses of all known biological systems. Among other functions, they are the motors that cause muscle contraction, the catalysts that drive life-sustaining chemical processes, and the molecules that hold cells together to form tissues and organs.

The following is a list of a few of the diverse biological processes mediated by proteins:

• Proteins called enzymes catalyse vital reactions, such as those involved in metabolism, cellular reproduction, and gene expression.
• Regulatory proteins control the location and timing of gene expression.
• Cytokines, hormones, and other signalling proteins transmit information between cells.
• Immune system proteins recognize and tag foreign material for attack and removal.
• Structural proteins prevent cells from collapsing on themselves, as well as forming large structures such as hair, nails, and the protective, largely impermeable outer layer of skin. They also provide a framework along which molecules can be transported within cells.

The estimate of the number of genes in the human genome has been changing dramatically since it was annotated (the latest gene count estimates can be found in this Wikipedia article on the human genome). Each gene encodes one or more distinct proteins. The total number of distinct proteins in the human body is larger than the number of genes due to alternate splicing. Of those, only a small fraction have been isolated and studied to the point that their purpose and mechanism of activity is well understood. If the functions and relationships between every protein were fully understood, we would most likely have a much better understanding of how our bodies work and what goes wrong in diseases such as cancer, amyotrophic lateral sclerosis, Parkinson's, heart disease and many others. As a result, protein science is a very active field. As the field has progressed, computer-aided modeling and simulation of proteins have found their place among the methods available to researchers.

An amino acid is a simple organic molecule consisting of a basic (hydrogen-accepting), amine group bound to an acidic (hydrogen-donating) carboxyl group via a single intermediate carbon atom: During the translation of a gene into a protein, the protein is formed by the sequential joining of amino acids end-to-end to form a long chain-like molecule, or polymer. A polymer of amino acids is often referred to as a polypeptide. The genome is capable of coding for 20 different amino acids whose chemical properties depend on the composition of their side chains ("R" in the above figure). Thus, to a first approximation, a protein is nothing more than a sequence of these amino acids (or, more properly, amino acid residues, because both the amine and acid groups lose their acid/base properties when they are part of a polypeptide). This sequence is called the primary structure of the protein. The Wikipedia entry on amino acids provides a more detailed background, including the structure, properties, abbreviations, and genetic codes for each of the 20 common amino acids.

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. Tertiary structure refers to structural elements formed by bringing more distant parts of a chain together into structural domains. The spatial arrangement of these domains with respect to each other is also considered part of the tertiary structure. Finally, many proteins consist of more than one polypeptide folded together, and the spatial relationship between these separate polypeptide chains is called the quaternary structure. It is important to note that the native conformation of a protein is a direct consequence of its primary sequence and its chemical environment, which for most proteins is either aqueous solution with a biological pH (roughly neutral) or the oily interior of a cell membrane. Nevertheless, no reliable computational method exists to predict the native structure from the amino acid sequence, and this is a topic of ongoing research. Thus, in order to find the native structure of a protein, experimental techniques are deployed. The most common approaches are outlined in the next section.

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:

Most of the protein structures discovered to date can be found in a large protein repository called the RCSB Protein DataBank (PDB). The Protein Data Bank (PDB) is a public domain repository that contains experimentally determined structures of three-dimensional proteins. The majority of the proteins in the PDB have been determined by x-ray crystallography, but the number of proteins determined using NMR methods has been increasing as efficient computational techniques to derive structures from NMR data have been developed. A few electron diffraction structures are also available. The PDB was originally established at Brookhaven National Laboratory in October, 1971, with 7 structures. Currently, the database is maintained by Rutgers University, the State University of New Jersey, the San Diego Supercomputer Center at the University of California, San Diego, and the National Institute of Standards and Technology. The current number of proteins (and/or nucleic acids) in the PDB database is displayed at the top-right corner of the main PDB page. The imaging method statistics of these structures (i.e., which methods were used for what fraction of the structures), as well as other classifications, can be found here. The European Bioinformatics Institute Macromolecular Structure Database group (UK) and the Institute for Protein Research at Osaka University (Japan) are international contributors to the contents of the PDB.

Numerous tools are available for visualizing the structures stored in the PDB and other repositories. Most such tools allow a detailed examination of the molecule in a variety of rendering modes. For example, sometimes it may be useful to have a detailed image of the surface of the molecule as experienced by a molecule of water. For other purposes, a simple, cartoonish representation of the major structural features may be sufficient.

A Few Molecular Visualization Programs

• Visual Molecular Dynamics (VMD) was originally developed for viewing molecular simulation trajectories. It is a very powerful, full-featured, and customizable molecular viewing package. Customization is available using Tcl/Tk scripting. Information on Tcl/Tk scripting can be found at this Tcl/Tk website.
• PyMol is an open-source molecular viewer that can be used to generate professional-looking images. PyMol is highly customizable through the Python scripting language.
• Protein Explorer is an easy-to-use, web browser-based visualization tool. Protein explorer is built using the MDL Chime browser plugin, which in turn is based on the RasMol viewer. Because Chime only works under Windows and Macintosh OS, the use of Protein Explorer is restricted to those platforms.
• JMol is a Java-based molecular viewer. In applet form, it can be downloaded on-the-fly to view structures from the web. A stand-alone version also exists, which can be used independently of a web browser.
• Chimera is a powerful visualizer and analysis tool that can be comfortably used with very large molecular complexes. It can also produce very high-quality images for use in presentations and publications.