Structural biologists and chemists have long held access to powerful computational resources for molecular visualization. Nevertheless, biologists outside of structural studies endured more primitive means of investigating and teaching about the structure-function relations of macromolecular machines. Many of us remember painful first attempts - by ourselves and our students - to fuse two-dimensional stereo views into three-dimensional structures, but we also remember the thrill of success and the striking beauty of these images, once attained. Despite the continued utility of stereo images in print articles, nonstructural biologists longed for computer visualization resources that would provide interactive investigation and presentation of macromolecules. Fortunately, a variety of free software for molecular visualization emerged over the past decade, and those of us in fields other than structural biology can now easily exploit these for research and teaching.

Roger Sayle's RasMol (Raster Molecules) 2.4, introduced in 1994, provided the first freely available, interactive program that allowed the viewing and manipulation of molecules on a desktop computer. RasMol was used widely in teaching and research. In addition, a generous contribution from Sayle and Glaxo Wellcome put RasMol's source code in the public domain, which permitted continued improvement and embellishment by other workers.

Recent versions of RasMol, including 2.7.1, let users view a variety of molecular structure files, including the popular Protein Data Bank (PDB) format. This program opens molecular-viewing and command-line windows. An extensive set of RasMol commands can be entered into the command-line window to render the molecule as the viewer sees fit, including selecting and modifying atoms, groups, or chains. One can save a series of commands as a script file to be invoked as needed. In addition, extensive documentation on RasMol commands is available for each version. Various versions of RasMol remain in wide use on a variety of platforms, which is testimony to its power and ease of use in research and in teaching.

In recent years, investigators built several powerful programs from RasMol source code. For instance, Windows users can experiment with RasTop 1.3 - a user-friendly, graphical interface to RasMol that eliminates typing in commands. For a casual or novice user of RasMol who has not memorized large portions of the RasMol manual, this is especially helpful and empowering.

RasTop provides an extensive set of menu commands that are transferred automatically to a molecule. It also allows multiple modes of selecting atoms, including selection by lassoing them on screen, which is not available in command-line versions. Other useful features come from a taskbar, where a button's function is explained by a pop-up window when the cursor passes over it. One can copy and paste selections of atoms, chains, and molecules to and from the Windows clipboard, and save all user-defined atom sets. Overall, RasTop makes macromolecular exploration more pleasurable for many biologists. This new interface is highly recommended for longtime RasMol fans and novices alike.

MDL Information Systems' Chime - another relative of RasMol - allows for the viewing and manipulation of molecules directly in a Web browser (Netscape is more Chime-friendly than Microsoft Internet Explorer). With this program, users interact with a molecule through a series of straightforward menu choices. Supported file types, including PDB, can be viewed from local sources or provided for Internet access by appropriately configuring your server, which you can read about at Chime Frequently Asked Questions.

The number of Chime molecular exhibits on the Web is growing rapidly, as you can see at Chime Great Sites and the World Index of BioMolecular Visualization Resources. In addition, I recommend using the construction of Chime molecular exhibits as a pedagogical tool, because students must gain an in-depth understanding of the structure-function relations of a particular molecule before they can construct a quality Chime Web page.

Protein Explorer (PE) is described as a "RasMol-like interface implemented in Chime." PE supports nearly all of the RasMol and Chime commands. Version 1.71 beta of PE - just released - offers a plethora of automated manipulations of molecules. Consequently, PE also makes visual exploration of protein structures more accessible to novices, and it is also useful for experts. I cannot go over all of PE's capabilities, but I must mention that the contact-surfaces option in the advanced mode of PE produces spectacular views of intermolecular interactions. This feature, coupled with PE's noncovalent-bond finder, allows students and experts alike to investigate weak interactions at the heart of macromolecular structure. Another advance is the multiple-sequence-alignment tool, which permits the visualization of conserved residues of homologous structures. Overall, PE is a powerful addition to the suite of RasMol-based programs.

There are also very useful, free molecular visualization and modeling programs that are not derived from RasMol. For example, the Swiss-PdbViewer is impressive. It provides an intuitive interface that allows users to view multiple structures simultaneously, construct models from amino acid sequences, search for hydrogen bonds, and view electron-density maps from crystallographic data. Multiple-sequence alignment and superimposition of multiple sequences also allow homology comparisons. The Swiss-PdbViewer page is linked to Swiss-Model - described as "an automated comparative protein modeling server" - which enables the construction of a structural model for a protein sequence, provided a homologous reference structure is available.

There are other freeware packages that produce stunning molecular images and employ a variety of rendering options not found in some of the RasMol derivatives. A few are gOpenMol, ICMLite, MOLMOL, Visual Molecular Dynamics, and WebLab ViewerLite. Like Swiss-PdbViewer and later versions of RasMol, these provide ray-traced files for publication-quality images. A site called Output Quality supplies a "judge for your own eyes" comparison of some of these programs. Unlike RasMol and its derivatives, these programs are not restricted to visualization, because they also allow for computational chemistry and molecular dynamics simulations, including ligand docking. In certain cases, simulations can be saved as movies. These programs are intended mostly for advanced users.

Of course, some commercial programs (e.g., Insight II) can perform all of the functions (and more) of the freeware mentioned above. Given the power of some of the freeware visualization resources just described, though, readers can try some of these before investing in expensive software. We are fortunate, indeed, to have free access to both an exponentially growing database of macromolecular structures and a variety of freeware to visualize them.