Notes from the Molecular Classroom

The goal of the Molecular Workbench projects, funded by the National Science Foundation, is to provide a rich environment that makes the atomic level familiar, predictable, and connected with the macroscopic world, and to understand the effect of such an environment on student learning. Keep up with our research and software in these short announcements and see our website for additional information.

Improved Learning, Improved Software

Analysis of data from the Molecular Workbench project reveals that high school biology students learn well when they explore and interact with a dynamic model of protein code and shape. Interviews conducted with students several months after the activities were implemented suggest that students maintain a strong mental model of this content long after the activities were introduced.

Molecular Workbench materials – including a computer model and the related “From DNA to Protein Conformation” curriculum unit (see below) – were tested in six classrooms in three suburban high schools in Massachusetts. In all classes, students scored significantly higher on the post-test than the pre-test. For instance, students regularly employed the ways in which specific amino acid properties (e.g., charge and hydrophobicity) help describe the interactions of the different amino acids with each other and with the solvent. Additionally, students correlated how a change in the sequence of DNA could have implications for protein function and, in some cases, for human health.

From DNA to Protein Conformation

This four-part unit offers the following scaffolded learning activities:

• Activity One – How a Protein Gets its Shape: Charged Amino Acids
• Activity Two – How a Protein Gets its Shape: Interacting with Water or Lipids
• Activity Three – How a Protein Gets its Shape: The Role of DNA
• Activity Four – Protein Malfunction and Disease

Students manipulated a computer model, built on a powerful computational “molecular engine.” With simple computer keystrokes and mouse clicks, students modified a model amino acid sequence. For example, they substituted and deleted nucleotides in the DNA, and observed the effects on the sequence of amino acids and the spatial organization of the protein. Students worked with a model segment of Sickle Cell hemoglobin. (See “Monday’s Lesson: Modeling Mutations,” page 6, for a similar activity.)

Figure 1. Teachers and students can explore a large molecule such as chlorophyll – the basic pigment of plants’ photosynthetic system – from various perspectives, starting with traditional “atoms and bonds” view (A) to its carbon skeleton (B) or a surface view (C).

Figure 2. An annotated image in the Molecular Viewer (tube view of trypsin).

Figure 3. A molecular dynamics simulation of intermolecular interactions in aqueous solution. The smaller circles represent hydrogen atoms, the larger, oxygen atoms; and the kidney-shaped object represents a macromolecule. The plus and minus signs on the macromolecule signify that it is polar. The dotted lines show the hydrogen bonds. Such a simulation may help students understand how water mediates chemical reactions between proteins.

Figure 4. A folded conformation of a 94-residue protein in an aqueous solution. The light beads represent hydrophobic amino acids. The darker beads represent hydrophilic amino acids. The black lines between two adjacent beads represent peptide bonds. The hydrophilic amino acids tend to be found on the exterior of the protein structure, where they make more contacts with water molecules.

The Molecular Viewer

Our 3D Molecular Viewer software is currently in development. This powerful and user-friendly software is written in Java and is cross-platform (Windows and Mac OS); it is designed to work with other software, including the Molecular Workbench. The Molecular Viewer is translated into five languages.

With the Molecular Viewer, users can explore preloaded molecules or download PDB (Protein Data Bank) files from the Internet, and view the molecules in a variety of representations, including color coded by individual atom and surface view (see Figure 1). The software is equipped with an interactive Periodic Table (which plays “periodic” music tunes!) and an amino acid reference data-table.

The Viewer also allows students to add notations to the molecular images, and save them for assessment or further reference (see Figure 2).

Molecular Workbench Drawing Tool and Arbitrary Shapes

Biological shapes are organic; they need to “breathe” as they move.  Recognizing the difficulty in building an analytical model for interacting particles with arbitrary shapes that is also computationally efficient, we developed a drawing tool in Molecular Workbench, which permits users to draw arbitrary non-self-crossing shapes, such as rectangles, ellipses, cubic splines, or free-form curves.

When the user finishes drawing a shape, Lennard-Jones particles are automatically aligned along the line if the shape is open, or along the border if the shape is closed, to its full length. After the alignment is completed, harmonic forces are used to connect the LJ particles in radial and angular directions, to combine them into a single object.

Such an object has a van der Waals surface that can attract (and be attracted to) other similar objects or LJ particles. It also has a border that is formed by the repulsive core of the Lennard-Jones potential to prevent overlaps with another object or LJ particle. If an atomic probe were used to scan over the border, an enveloping shape would be created, because the repulsive cores push back on the probe. In molecular biology, such an enveloping shape generated by a real or hypothetical probe is called a molecular surface.

A molecular surface object is not a rigid body. Its shape vibrates and can be distorted. The harmonic forces used to bind the LJ particles form a “spring chain” that maintains the shape. The rigidity of the shape rests on the strength of the harmonic forces.

The molecular surface object models a macromolecule (e.g., proteins) in a simplified way. It captures the essential idea that the surface of a macromolecule is generally far more important than the interior in facilitating intermolecular interactions and active site reactions. For example, a MD simulation for the intermolecular interactions of macromolecules in aqueous solution, in which the macromolecules are represented by molecular surface objects (see Figure 3), shows clearly the interactions between the charged sites and water molecules around them.

Molecular Workbench
Software: Additional Enhancements

Recent work on the Molecular Workbench software has also enhanced its capacity by increasing the number of objects, including amino acids (see Figure 4), and building in the ability of authors to annotate their models, as well as build full activities around the models. The software authoring interface, designed for non-programmers, allows the user to insert interactive models (not just molecular simulations) and their supporting interactive components, such as bar graphs, sliders, buttons, text boxes, tables, and so on, into a word processor. The word processor hosting environment also offers the user a full set of traditional text editing functions (including the ability to insert images and add hyperlinking, for example). A chemistry engine has been added and activities using the engine are being written in WISE, the learning environment developed at the University of California at Berkeley.

Molecular Workbench Workshops

The Molecular Workbench projects offer workshops for secondary and college level science educators on using and authoring with their software. A workshop is planned for June 24-25 at the Concord Consortium in Concord, Massachusetts. If you are interested, please contact Barbara (barbara@concord.org).