Structural computational biology: introduction and background  (Page 4/6)

Structure prediction of large complexes

Large macromolecular complexes and molecular machines present a particular challenge in structure determination. Generally too large to be crystallized, and too complex to solve by NMR, determining the structure of these objects usually requires the combination of high-resolution microscopy combined with computational refinement and analysis. The main techniques used are cryo-electron microscopy (Cryo-EM) and standard light microscopy.

Protein structure repositories

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-dimensionalproteins. The majority of the proteins in the PDB have been determined by x-ray crystallography, but the number of proteins determined using NMRmethods 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 7structures. Currently, the database is maintained by Rutgers University, the State University of New Jersey, the San DiegoSupercomputer 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 forProtein Research at Osaka University (Japan) are international contributors to the contents of the PDB.

Visualizing protein structures

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.