Student Manipulation of 3D Representations of Proteins One of the major concepts outlined in our Biology Concept Framework that we wished to teach the students in Introductory Biology was: "At the molecular level, biology is based on three-dimensional interactions of complementary surfaces." However, we have found that two-dimensional cartoon representations of proteins fail to convey the three-dimensional interaction of proteins. We wished to find ways to give students a better "feel" for what proteins look like and how they interact with each other. We therefore began the two projects described below.

The "Shape Game" effort led by Julia Khodor and Dina Gould Halme We wanted the students to have the opportunity to hold a three-dimensional object in their hand and see what happens when it interacts with other three-domensional objects. The first version of the game involved using small hand-made clay objects representing tertiary and quaternary structure of protein complexes. The students were given multiple versions of each subunit with the key regions colored to represent their charge or hydrophobicity. The students were asked to make sets of complexes with the subunits and answer a series of directed questions to help them understand that: (1)binding is the mechanism by which all information is transmitted; (2)change in shape can prevent binding and therefore affect function; (3)complementary mutations that restore binding can restore function; and (4)proteins must maintain shape with respect to the next binding partner (point of transmission of information) in order to maintain function. The rudimentary version of the Shape Game was a prototype, the purpose of which was to determine whether this was indeed a good approach to teach the four concepts above and to figure out what works and what doesn't. Our anecdotal evidence from discussions with students showed that they did appreciate the concepts. However, they felt that the 2D representation was too simple, and not challenging enough for them. Shape Game Lesson

Pieces of the first Shape Game with color labeled regions of charge and hydrophobicity, note that they are essentially 2D.

Improved 3D version of Shape Game Over Devember 2003 and January 2004 we were able to design and have produced plastic, three-dimensional version of the game. That version was used in the Spring 2004 7.014 class, as well as in the Fall 2004 Voluntary Lab. The response from students in the latter course was very positive. The correct way to assemble complexes out of the three-dimensional pieces is not as immediately obvious as was the case for the prototype game pieces. This seems to have resulted in students feeling that they got more out of the experience.

Computer models used to create the molds in which the plastic shape game pieces were made. The image on the left is of the whole complex, the one on the right shows an internal surface.

Pieces of the second version of the Shape Game showing the color labeled regions of charge and hydrophobicity

Computer-Based Representation and Manipulation effort led by Julia Khodor We wanted to give our students a better sense of the three-dimensional structure of proteins than they have been able to get in the past. After reviewing various protein structure viewers commonly used in education, we decided to try using a more sophisticated viewer so that our MIT students could control what they saw and also so that we could take advantage of some of the more powerful features that are available in these programs. We therefore designed a problem set that required our Introductory Biology students to utilize the Swiss Protein Viewer. There vere 5 versions of the problem set, and there was also a follow-up problem set that tried to connect protein features to molecular biology features of the gene encoding that protein. A survey indicated that many students responded very positively to the experience of being able to actually manipulate protein structures in 3D. However, it was also unambiguously clear that the complicated interface of the Swiss Protein Viewer makes the program far too cumbersome to be used directly in this type of educational application. This experiment precipitated a series of discussions with various people, for example the Harvard Medical School crystallographer Tom Ellenberger and Helen Berman at the Protein Data Base, about the possibility of designing progressive/scalable overlay interfaces for such research-level 3D structure viewers to make them useful for education. The Protein Data Base sent Shuchismita Dutta up to MIT for a day to discuss our ideas and this, in turn, has led to an invitation to Julia Khodor to attend a workshop on "Visualization of Biological Complexes" being held in California in October 2003. This is a very interesting issue with much potential, since designing progressive/scalable interfaces for research-level biology visualization programs of all sorts would not only make them accessible for education applications, but would also make it easier for new users, at all levels, to learn to use these powerful but complex programs. Julia Khodor adapted some of the problem sets to be used in a session of the High School Field Trip to MIT. She worked with the students along with Shannon Flaugh. although the students expressed great interest in seeing the 3D stuctures of the proteins and being able to manipulate them, the computer program proved much too combersome to be used in a classroom setting. HS Field Trip Lesson Plan

3D Visualization Outreach Activities effort led by Melissa Kosinski-Collins, Shannon Flaugh, and Jonathan King Further efforts aimed at harnessing the power of protein structure manipulation software in education have been the focus of members of Jonathan King's lab as well. Melissa Kosinski-Collins and Shannon Flaugh originally began by tutoring a group of 12 area high school teachers in the visualization of protein structure using the SwissPDB Viewer individually and soon realized that the complicated user interface of this software was too complicated for the novice user. Melissa and Shannon then designed a set of explicit written interactive excercies for students and teachers emphasizing the relationship between protein structure and function using the SwissPDB Viewer. Due to the complexity of the program, two sets of instructions were prepared, an advanced and a beginners' version. The exercises were tested on group of area high school students in the TEAL classroom at MIT. This classroom allowed a master computer controlled by an experienced instructor to be projected on a central screen. In addition, each group of two students had their own laptop computer on which they could manipulate the structure of a protein right along with the instructor. Despite the detailed written instructions and the presence of a master computer, the students still became lost in the complexities of the SwissPDB viewer. They often selected the wrong item and were forced to close the program and restart to continue following the protocols. Ultimately, the exercise required a 6:1 student to teacher ratio, and is impractical for the typical classroom setting. Click here to see more pictures of the TEAL classroom and students at work. Student self-led tutorial Teacher-moderated tutorial

Future Directions for the 3D Visualization Project The individual efforts of the HHMI education group and of the King lab have now been united into a collaboration to create an accessible software for visualizing protein structure. We plan to create the actual program based on the source code from VMD and design a series of interactive modules to be used with this software for various levels ranging from high school to college. We have applied for iCampus funding to support this work.