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" 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

The Use of 3D in the Biology Undergraduate Laboratory Course effort led by Melissa Kosinski-Collins The Biology Introductory lab course is divided into four sections, one of which is Protein Biochemistry. The biochemistry module of the class focuses mainly on purification and identification of recombinant beta galactosidase protein. Although the students are asked to work with the protein in the laboratory section of the course, they never see a manipulatable 3D image of the protein in lecture or in lab. Melissa has created simple and straight-forward exercises for the students that involve the visualization of the the different levels of structure of beta glactosidase, as well as exercises that explore its active site. 7.02 Class Website Beta Galactosidase Worksheet Beta Galactosidase Surface Character Beta Galactosidase Tertiary Interactions Beta Galactosidase Complex with Lactose Beta Galactosidase Complex with ONPG Beta Galactosidase Complex with IPTG

The Use of 3D in the Introductory Biology Course effort led by Melissa Kosinski-Collins and Julia Khodor Melissa has designed several interactive protein structure viewing modules that allow students to visualize proteins in 3D using a program called "jmol". The exercises are relatively simple and allow students to explore the muliple levels of protein structure in class or at home. Although student-initated questioning is limited in this format, the students can explore the structures at a personal pace and do not become lost in complex controls. The students first saw the program in TA-led recitation sections. Julia and Melissa wrote a problem that was discussed in section. The question incorporated different aspects of protein structure and side chain interactions while leading students through a guided tour of a protein important in human disease known as Cystathionine Beta Synthase (CBS). The students were then asked to explore the structure of another protein, human gamma crystallin, at home in their problem set. Word documents of both the section problem and the problem set tutorial are accessible below. There is also a link to the introductory biology course website where the structure modules are located. Problem Set: Crystallin Recitation: CBS Link to Intro Bio Course Structure Modules CBS Applet Crystallin Applet

The TEALSim PDBViewer In the summer of 2005, a three-way collaboration was begun to create a new, intuitive piece of software that would allow students to learn about biological molecules in 3D. Graham Walker and Meliss Kosinski-Collins of the HHMI Education Group, John Belcher, Mike Danziger, and Andrew McKinney of the MIT physics department, and Charles Schubert from the MIT academic computing department joined forces to create a software that would teach 3D structure to biology students from a pedagogical stand-point. The rationale behind the software was to create a system that introduced students to biomacromolecular structures in the same way in which they would be presented in a classroom environment. The program needed to provide students with manipulation capabilities, while still maintaining a useable interface. Using her knowledge of protein structure and function and her experiences in the classroom, Melissa chose the various functionalities of the program. Mike Danziger, Andrew McKinney and Chuck Schubert were able to take Melissa's ideas and computationally mold them into a usable program. The three programers are primarily responsible for making the vision of the PDBViewer a computational reality. The TEALSim PDBViewer software was built upon the TEALSim architecture. TEALSim is a open-source software designed here at MIT that was orginally used to allow students to see complicated physics simulations and manipulations in 3D. John Belcher, a professor in the MIT department of physics was primarily responsible for initiating the efforts to design TEALSim. An early version of TEALSim PDBViewer was tested during the 2006 high school field trip to MIT using a guided inquiry program called Mastering Physics. John took the questions and activities for viewing hemoglobin and porin in 3D in earlier field trips and wrote a series of modules in Mastering Physics that used the new program. Since then, the team has made several upgrades to the program and plans to increase functionality in time. Recently, Mike agreed to stay at MIT to pursue his masters and comtinue to work on this project. The TEALSim PDBViewer is an open-source free software that is constantly evolving. It is freely available on the web.