The Role of Jmol/JSmol in Teaching about Proteins

I teach a course devoted to one type of biomolecule: Proteins. The course is The Biology and Biochemistry of Proteins, Biol 443.

Biol 443 is a digital-rich course designed to use the wealth of information available on-line to study the structure, function and evolution of proteins. There are literally scores of online databases and analytical tools available to scientists to study proteins, and many of these are used by students in Biol 443 to study the biology and biochemistry of proteins. In my continual effort to expand digital communication in my courses, I require each student in Biol 443 to use these on-line databases and analytical tools, as part of a semester-long research project, to study the structure, function and evolutionary history of an assigned protein and develop a lengthy, detailed final report of their work.

I chose to develop a course on proteins because many scientists, including me, regard the study of protein structure, function and evolution as a study of life itself. Proteins are the heart of living systems. They play the central role in nearly every cellular process. They are, quite literally, organic molecular machines - molecular devices that serve as the machinery of life.

Describing proteins as machines is not hyperbole. Take, for example, the protein shown to the right, ATP synthase. ATP synthase is a large complex protein that synthesizes ATP, the cell's primary source of organic chemical energy. ATP synthase requires a source of energy to synthesize ATP, and that source of energy is the energy found in a hydrogen ion (proton) gradient. The protein works exactly like a hydroelectric dam. Where a hydroelectric dam converts the energy from flowing water into electrical energy, ATP synthase converts the energy from flowing hydrogen ions into the chemical energy found in ATP molecules. In fact, the basic structure of ATP synthase is very similar to that of a hydroelectric dam. Hydroelectric dams have water channels, turbines, and generators. Water flows through the channel, which then funnels water flow through and powers the rotation of a turbine. The rotating turbine in turn rotates the shaft of a power generator, which in turn creates electricity. Similarly, ATP synthase has a molecular hydrogen ion channel, a molecular turbine and a molecular generator. Hydrogen ions flow through the molecular channel, which then powers the rotation of a molecular turbine. The rotating turbine in turn rotates the shaft of a molecular generator, which in turn synthesizes ATP.

Protein Scientists Strive to Determine the Structures of Proteins

One lesson we can learn from our brief look at ATP synthase is something that is true for all proteins: a protein's structure reflects its function, and an understanding of a protein's structure is key to understanding how that protein works. Therefore, protein scientists strive to determine the detailed structures of proteins.

One method scientists use to determine a protein's structure is xray crystallography. In xray crystallography, a beam of xrays is targetted through a crystal of a protein, resulting in the diffraction of the xrays, producing a diffraction pattern. Analysis of the diffraction pattern provides scientists with the 3-dimensional positions of the atoms in the protein crystal, the physical characteristics of their chemical bonds and other information.

Once collected and published, the spatial information obtained about the structure of the protein is deposited in one of several on-line protein data banks, such as the RCSB Protein Data Bank (PDB). The RCSB PDB is the major on-line repository for the three-dimensional structural data of large biological molecules. Its current holdings total 100,843 molecular structures, with over 93,000 of those being protein structures. The spatial information for each of these structures is freely available for download and use. One of the files the RCSB PDB has in its archive contains the structural information for ATP Synthase. The file that contains the coordinate locations of each atom is simply a text file that can be downloaded here and opened on any computer using any simple text editor.

The Digital Visualization of Protein Models Using Jmol/JSmol

It's obvious that obtaining protein structural information has limited value if the protein structure cannot be visualized. Thus, the digital visualization of protein structures has been an active area of interest since the 1960s. Over the past 20 years, researchers have developed several molecular graphics tools that use the data from PDB files to display models of protein structures and empower the user to manipulate those models to study the molecular details of the protein's structure. One of these molecular graphics tools is Jmol. Jmol is a free, open source, cross-platform Java-based molecular viewer used to embed dynamic three-dimensional models of chemical structures and biomolecules into web pages. It has become one of the most popular molecular viewing tools. JSmol is a fully functional Javascript-based implementation of Jmol that works with HTML5 and does not require Java. By using the Javascript-based scripting language of JSmol, students, educators, and researchers can construct models of proteins, display these models on-line, and write scripts that enable users to explore a wide variety of structural and biochemical features of a protein, including animations that can be used as choreographed tours of the model.

A demonstration of what JSmol can do is provided here. Below is a model of ATP synthase, embedded in this web page using JSmol. The raw data that produces the model comes from the protein databank text file for ATP synthase, mentioned above. The model's overall appearance, including the colors, orientation and spin, are all dictated by a JSmol script running in the background. This script freshly loads each time this page is refreshed. If you so desire, refresh the page now and watch the script load below.

As the model of ATP synthase spins, you can gain an appreciation for the complex 3-D structure of the protein. Each colored strand represents a separate amino acid chain. There are 18 separate amino acid chains in ATP synthase, folded and assembled in a specific complex way to give the protein its final 3-D structure. Follow the instructions below to examine just a few of the simple structural features of this protein. As you read the instructions, click on the underlined links.

  • 1. First, let's highlight each of the 18 individual amino acid strands that make up the protein.
  • 2. These 18 amino acid chains are grouped into three major domains. One of these domains is the so-called FO Domain. The FO domain consists of 10 helical amino acid chains that form a cylinder (the turbine). Down the center of the turbine is a hydrogen ion channel. As hydrogen ions pass through the channel (away from you and into the depths of the protein), the energy of that hydrogen ion flow powers the rotation of the entire cylinder (the turbine).
  • 3. As the turbine rotates, its rotation powers the rotation of the second domain, the so-called axle domain. The axle domain consists of 4 helical amino acid chains that form the shaft of the molecular machine.
  • 4. The shaft rotates within the stationary generator, the so-called F1 domain. The F1 domain is a large enzyme complex, made up of 6 large, mostly helical amino acid chains, that synthesizes ATP. The energy needed for this synthesis is provided by the rotation of the shaft, which is in turn powered by the rotation of the turbine, which is in turn powered by the hydrogen ion flow. As the shaft rotates within the center of this generator, the shaft interacts with each of the six amino acid chains. For every approximately 2 rotations of the turbine and shaft, the F1 domain synthesizes approximately 3 ATP molecules.
  • 5. Reset to original orientation.

This demonstration touches on only a few of the many structural features JSmol can reveal about a protein. JSmol can expose specific amino acids within an amino acid chain, it can show a specific atomic bond within a protein, it can open the protein and zoom in on a binding site, it can reveal the specific molecular interactions involved in a protein's function and so much more.

JSmol also empowers the viewer to manipulate the model with the mouse or keypad, something you can do right now. First, Reset the protein to its original orientation. Right click while moving the mouse enables you to rotate the model in any direction. Shift + right click while moving the mouse will enable you to zoom in and out.

Jmol/JSmol in the Classroom

There are a wide variety of molecular viewers available to students and faculty to study the structure of proteins, and for years my students and I have been using a variety of powerful molecular viewers, specifically Protein Workshop, Simple Viewer and Kiosk Viewer, to view and study models of protein structures in the classroom. Each of these viewers provides very nice visualization of protein models and empowers students to more thoroughly study the structural features of proteins. I use these viewers during lecture to show aspects of the structure of specific proteins, and my students use these viewers to generate static images of their assigned protein as they work on their semester-long project and prepare their final written research reports. However, these viewers are proprietary viewers: they can only be used within the RCSB PDB website. Therefore, they cannot be used to embed dynamic models of proteins into web pages, as is done here with JSmol, thus limiting students in how they present models of proteins in their reports. Rather than create digital reports that include dynamic models that can be manipulated and animated, students have been developing traditional (non-digital) written reports that include static images of protein models.

All of that can change with the use of JSmol in the classroom. Empowered by JSmol, students will have a more compelling reason to develop digital reports that include the same kind of dynamic presentation of a protein model used here, thus improving the effectiveness of their reports as teaching and learning tools and making their reports widely available to the public via the internet. Therefore, my next step in the development of digital communication in my classes is to incorporate the use of JSmol in all aspects of Biol 443: to incorporate JSmol driven models in lecture, to incorporate a series of lessons for students on how to use JSmol, and to require students to develop digital reports that incorporate, among other things, dynamic protein models displayed through the use of JSmol.

Copyright © 2011 by Stephen Gallik, Ph. D.