Test Platform

Pentium II 450 MHz processor running Windows 98 with 128 Mb RAM

Overview

MOLE, from Applied Thermodynamics, is a molecular graphics package for Microsoft Windows 95/98 or Windows NT. MOLE is designed to visualize, analyze, and study the molecular structures from Brookhaven National Laboratory Protein Data Bank (PDB) files. The program is easy to use and provides high quality, high performance molecular graphics and modeling solutions for Windows-based computers. MOLE offers some impressive features that are normally found in molecular graphics packages for Unix workstations. With MOLE, one can use structure data to calculate various molecular parameters. The program also allows one to design one's own approaches to the study of protein structure.

Users can either print out high quality images from MOLE, or simply copy/load them into other Windows programs. With Open Automation Interface, users can even implement custom solutions and calculations using any other programming environment that supports OLE automation methods. MOLE is an ideal molecular structure software tool for researchers who are not specialists in protein structure modeling.

Program Features

MOLE is a molecular structure visualization, modeling, and analysis program. It uses data from the Brookhaven National Laboratory Protein Data Bank (PDB), an archive of data that resolves three-dimensional structures of proteins, nucleic acids,and other macromolecules.

MOLE provides several impressive features that make it quite unique. First, it makes it easy to create graphic images, and 3-D graphic capabilities are excellent. Second, one can embed molecular graphics created in other programs, such as Microsoft Word and Excel. MOLE also provides researchers with a simple way to estimate structural parameters including dihedral angles, hydrogen bonds, Van der Waals interactions, solvent accessible surface area, and packing of the protein interior. Finally, MOLE enables one to create custom solutions and calculations using other programming environments that support OLE automation methods, such as Visual Basic, Visual C++, or Borland Delphi.

Supported File Formats

MOLE can open PDB files (*.pdb or *.ent) directly from the File/Open menu command. After a PDB file is successfully loaded, MOLE displays it as a black wire frame with a white background. The File/Load PDB menu command loads the molecular structure data from the *.pdb file into an empty MOLE document. PDB files, which are compressed on two CDs, are included in the MOLE package. The built-in search browser makes it extremely convenient to use. You can use the File/Search PDB menu command to find an entry in the database. MOLE can search the Protein Data Bank according to component, class, biological source, and author.

One can save files in MOLE (*.m3d) format, which stores all of the structure information about the molecule, along with the styles and attributes of its graphics representation. MOLE can also save files in Joey 3d Viewer (*.j3d), metafile (*.emf), and bitmap file (*.bmp) formats from the File/Save Special menu command, as well as PDB files (*.pdb) from the File/Export to PDB menu.

Quality 3-D Display and Modeling

Creating and manipulating 3-D structures is very easy in MOLE. After structural data are loaded, the molecule structure will be rendered as a black wire frame over a white background. To view a more informative 3-D image, one needs to create molecule scenes from the View menu, or by clicking the Select Objects toolbar button. One can render the same molecules in a variety of styles, and one can view these images in separate windows and in different styles at the same time.

Figure 1 shows the structure of trypsin with inhibitor BPTI as a stick model, and figure 2 shows the secondary structures of the same protein. Figure 3 shows a space fill model of interleukin 1-b converting enzyme.

One can synchronize these windows by clicking the Synchronize Other Windows button, so that changing the viewing angle in one view will also result in the same changes in all other views. To create secondary structures of protein molecules, one selects Scene Wizard from the Scene menu, or clicks on the toolbar button to open the Scene Wizard window to set the styles and colors. This option allows users to draw a secondary structure in a few seconds. In addition, one can supplement the images with text labels positioned within 3-D space. All parts of the molecule can be assigned visual properties designating their color, reflectivity, and smoothness.

Manipulating images is straightforward in MOLE. First, one clicks the Camera On Left button, then any one of Translate, Zoom Camera, Rotate Objects, Orbit Camera, and Reset Camera buttons. Then, one uses the mouse buttons to move, zoom in and out, rotate (plane of the screen or in any direction), and reset the image very easily and quickly. By clicking on the Stereo button, one can view the stereo structure.

MOLE generates high quality and high resolution images. The rendering speed is very impressive, even with large molecules, and the program remains responsive to user commands even during the rendering time, making the application truly multitasking in the Windows environment.

From the Edit/Copy Special command, one can easily copy the selected image to other programs, such as Microsoft Word, with excellent publication quality 3-D images. Users are also able to print high quality images directly from MOLE.

Estimate Macromolecule Structural Parameters

MOLE can perform various calculations to estimate structure parameters. These calculations include accessible surface area (figure 4), hydrogen bonds (figure 5), dihedral angles, Van der Waals energy, and packing of protein interior. Figure 6 shows the accessible surface structure of lysozyme. To perform the calculation, one selects the Scene/Calculate menu command to open the specific parameter calculation window, and to select the subset of the structure to be calculated. One can send the results of these calculations directly to Microsoft Excel, and MOLE can visualize the calculation results. In this reviewer's opinion, this is one of the most impressive features of MOLE. For researchers who are not experts in crystallography or protein structural modeling, yet want to gain information on structural parameters of proteins, MOLE is the ideal software tool.

Design Custom Solutions

MOLE provides an Open Automation Interface to extend its functionality. This is a very attractive feature for users who can write their own programs and want to extend calculations with their customized algorithms. If users require features and methods not included in MOLE, they can design applications using other programming languages which support OLE automation.

MOLE recommends Microsoft Visual Basic as the programming language, and includes several sample programs written in Visual Basic. The manual includes an extensive set of examples showing how to use Visual Basic to design extension programs. MOLE can be a particularly useful tool for users who are interested in protein structure and function studies, and statistical mechanics of the molecules. One can view a very simple implementation of a contact map using Visual Basic extensions at the Applied Thermodynamics Web site.

Room for Improvement

Those who try MOLE will not find any obvious problems, although a couple of additional features would make the program more powerful and convenient to use. For instance, users do not have the ability to mutate residues, change bond length and angle, or dock the substrate/inhibitor. Although the ability to create custom solutions is an excellent feature, many MOLE users may not have strong enough programming backgrounds to make use of it. Providing built-in custom functions, such as application templates, would make it more convenient for users to develop their own applications.

The Bottom Line

MOLE is an excellent molecular modeling tool for the PC, with useful menus making it very easy to learn. Image rendering is fast and smooth. The quality of MOLE's images is very impressive. The features that calculate and visualize structural parameters are outstanding. MOLE provides an easy-to-use tool for estimating protein structural parameters. This unique feature gives MOLE an obvious advantage over many other molecular visualization programs. Custom Solutions offers a useful tool for users who can create their own applications to suit their needs.

The price of MOLE is quite reasonable, considering the features it offers. For any researcher who needs software to view molecular structures, estimate protein structural parameters, produce pretty pictures of molecular images, copy between Windows applications, produce publication quality graphics, and create customized application, MOLE is the perfect tool.

System Requirements

MOLE requires a PC-compatible computer running Microsoft Windows 95/98 or Windows NT. The minimum system requirements are an Intel 486/66 or higher processor, 16 Mb of RAM, and at least 256 colors for graphics purposes. The recommended configurations are a Pentium class processor, 32 Mb or more of RAM, and a 3-D accelerated video card. MOLE can run on the minimum configuration, but the recommended configuration vastly improves performance (especially for large macromolecules).

Purchasing Information

MOLE is available for $198.00 ($148.00 with academic discount and $98.00 for students) from Applied Thermodynamics LLC, 222 Schilling Circle, Suite 130, Hunt Valley, Maryland 21031-0157. Users can contact Applied Thermodynamics by mail, by phone at (410) 771-1626, by fax at (410) 771-1627, or by email. Visit the Applied Thermodynamics Web site to learn more about MOLE or to download the demo version of the program.