Jmol-Enhanced Biochemistry Research Projects - Journal of Chemical

May 20, 2011 - This project culminates with students preparing their own Jmol-enhanced Web site that both visualizes their chosen protein's structure ...
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Jmol-Enhanced Biochemistry Research Projects Matthew Saderholm* and Anthony Reynolds Department of Chemistry, Berea College, Berea, Kentucky 40404, United States

bS Supporting Information ABSTRACT: We developed a protein research project for a one-semester biochemistry lecture class to enhance learning and more effectively train students to understand protein structure and function. During this semester-long process, students select a protein with known structure and then research its structure, sequence, and function. This project culminates with students preparing their own Jmol-enhanced Web site that both visualizes their chosen protein’s structure and explains its function. All students were able to successfully produce a Web site regardless of prior experience. Compared with previous students who wrote a standard research paper, students involved in this project were more enthusiastic about biochemistry and ended the semester with a better appreciation of the connection between protein structure and protein function. KEYWORDS: Upper-Division Undergraduate, Biochemistry, Computer-Based Learning, Internet/ Web-Based Learning, Molecular Biology, Molecular Properties/Structure, Proteins/Peptides, Student-Centered Learning

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iochemistry has become an integral part of most undergraduate chemistry curricula.1 Although the value of biochemistry may be obvious to biochemists, it is not always clear to the undergraduates in the course. Many students find it difficult to keep up and to connect to the material as the course moves quickly. Similar to many schools, the biochemistry course at Berea College is a lecture-only class with no laboratory component. The one-semester course is usually taken in the third year by chemistry majors and other students interested in medicine or biomedical research. Although the biochemistry course has a two-semester organic chemistry prerequisite, there is no biology requirement. To keep students engaged, for the past eight years the biochemistry course has included a research project. Initially, students were required to select a protein with a known structure and prepare a final paper describing its structure and function. This project introduced them to the scientific literature and emphasized the value of research and writing in a science class. The research project has now evolved to include protein visualization and sequence analysis by incorporating student research papers and a Jmol-powered2 protein structure into their own Web page. This component was added to address a second challenge in teaching a course focused on the structure and function of biological macromolecules: training students to connect these massive structures to a defined function. Introducing students to protein structure through computer-assisted visualization in an introductory-level undergraduate biochemistry course can be challenging for a number of reasons. First, it is difficult because computerized classrooms need to be found for students to interact directly with visualization programs. Second, once such a classroom is found, time must be taken to train students to use the programs—even the straightforward Webbased programs such as FirstGlance3 have a learning curve. In our experience, these challenges are worth tackling. We have found that when students are directly involved in creating a Web site Copyright r 2011 American Chemical Society and Division of Chemical Education, Inc.

that explained their protein’s structure and function, they not only learn more about protein structure and its connection to function, they were also more engaged. The primary goal of replacing a research paper with a Web page was to allow students to integrate the initial project’s traditional paper structure in a more dynamic, engaging, and personalizable format. Because the Web page utilizes a Jmol-powered graphical interface for molecular viewing with a written paper describing the protein, the final product replicates protein structure tutorials currently found on many academic and textbook Web sites. The Web page design utilizes simple HTML,4 PHP,5 and Jmol or JavaScript2,6 to make the construction accessible to students with little or no previous experience using HTML or JavaScript. Style sheets7 can also be incorporated to add additional coherence to the set of student research pages. In our case, a style sheet was used to give coherence with the main chemistry department page. Jmol was used to visualize the protein structure for a variety of reasons, the most important being its stand-alone capability. To view the final Web sites, Jmol does not require the installation of any programs other than Java (a programming platform usually installed as part of the operating system). Jmol is a free molecular viewing program originally developed as an open source substitute for Chime.8 Second, Jmol was utilized because of students’ prior, hands-on experience with protein visualization using the Jmol-driven FirstGlance3 Web site early in the semester. Finally, Jmol-enhanced Web sites are straightforward to use and construct and allow for the visualization of nearly every kind of molecular representation that would be useful in an undergraduate biochemistry course. Other instructors have used Jmol effectively to facilitate student learning of molecular symmetry,9 organic molecule structure10 Published: May 20, 2011 1074

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Journal of Chemical Education and organic mechanisms,11 and biomolecular structure.1214 In terms of chemical research, McMahon and Hanson15 describe the recent trend among journals to use enhanced figures; however, we could not find other examples in which the students generated Jmol-enhanced Web sites. The closest examples we found that resemble our approach are Proteopedia,16 a wiki version of protein tutorials and a Chime-based project by Sears and Thompson.17 Proteopedia has similar advantages (access) and disadvantages (lack of editing control) of a wiki. In addition, the functionality of Jmol has been limited to a subset of basic functions. Sears and Thompson’s project similarly used file templates but did not incorporate a research paper and has not been migrated to Jmol. Steven Cammer’s SChiSM218 also allows for development of Jmol Web sites but emphasizes the Jmol component and does not allow for inclusion of student writing. The “Molecular Museum Exhibits” constructed by Marcy and his students19 are an excellent resource but again do not appear to connect the work to student research on particular protein’s function. Even though protein visualization is an essential component to our project, students spend more of their time researching the function of their protein. Our approach allows students to work interactively with their own project as well as expose themselves to active areas of research within biochemistry rarely discussed in the classroom. Unlike the initial, traditional written paper project, the Web page project is more dynamic, allowing students to connect protein function directly with protein structure. The Web site format has garnered positive feedback from the two classes of students involved in the project.

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Table 1. Graded Research Project Components Assignment

’ GUIDING STUDENTS IN WEB SITE DEVELOPMENT There was no expectation of prior Web site design experience. Students were able to construct a respectable final Web site with minimal training using the simple template we designed. After

Proposed pdb code20 posted on a

Protein Selection

classwide discussion board for public instructor approval to avoid overlapping requests Structure and Sequence Reports

See supporting documents for details

Annotated Bibliography

10-Source bibliography for their

Project Outline

electronic paper Proposed structure for their electronic paper as well as a description of what Jmol components they planned to use to help visualize their protein

Rough Drafts of Written Work

First draft of electronic paper assessed for by instructor for thesis and structural problems; revised second draft circulated

Rough Draft of Web site

for peer review Each student or group Web page reviewed by instructor first and then two other students second (after revision)

Final Draft

Editing access to the Web site closed and the final integrated project evaluated

Table 2. Tutorials for Students Tutorial

’ GUIDING STUDENTS IN SCIENTIFIC LITERATURE RESEARCH Components of the literature research process should be familiar to students. However, reading biochemistry research articles can be intimidating, so it was important to set clear and manageable goals for students to approach their protein research project. We divided the project into seven discrete assignments and provided voluntary out-of-class tutorial sessions to give students the opportunity to build new skills. The required submissions expected from each student or group are described in Table 1. As each of these required components were manageable and additive, students were able to keep up and assemble viable final projects by the end of the semester. Although the tutorial sessions set up outside of lecture were not required, they were well attended. The four tutorials, described in Table 2, were led in a classroom with Internet access for each student. ’ EXAMPLE OF A STUDENT WEB SITE Somewhat surprisingly, few students reported prior experience with Web design. To minimize student anxiety about the research process and the Web page construction, an example was provided that focused on the LOV domain from photoprotein 3.27 As can be seen from Figure 1, the structure for the Web site was straightforward.

Description

Description

Scientific Literature Searches

Librarian-led workshop on Scopus21 and general research skills

Structure Analysis

Eric Martz’s Protein Explorer22 protein tutorial was modified to work with the features provided through the Jmol-driven FirstGlance3 and the ConSurf29 server

Sequence Analysis

Protein sequence files were downloaded from the National Center for Biotechnology Information23 and Vector NTI Advance24 (license purchased through the KBRIN NIH grant to Kentucky colleges and universities) was used to access structure prediction algorithms.25 Students also submitted their protein to a BLAST26 search and analyzed the results

Web Site Design

Students worked one-on-one with the teaching assistant or instructor to learn how to construct simple Web sites using the provided framework

the tutorial session, students needed to provide the text files described in Table 3. Samples for these files are provided in the Supporting Information. Only two files, index.php and jmol.php, involved any “coding” by students. The only text that needed to be changed in index. php on a project-by-project basis was the Web page title and the paper title. The script also loads a links.php file containing the links at the top of the page and a contact.php file containing the departmental contact information at the bottom left that are loaded on each page. Although students needed to modify jmol. php more significantly, Jmol’s logical structure facilitated rapid 1075

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Figure 1. Screen shot of the LOV example page.28 The left frame is for protein structure with the upper left containing the Jmol structure, the middle left containing the configurable Jmol commands, and the lower left containing globally defined departmental contact information. The right panel, containing the student’s electronic research paper, scrolls to allow readers to continually interact with the structure while reading.

Table 3. Required Text Files Submitted by Students to Construct Their Protein’s Web Page File

Description

XXXX.pdb

Appropriate structure file downloaded

paper.html

from the RCSB Web site.20 Final research paper was saved in HTML format.

index.php

Template file downloaded and modified to change

Citations were expected to be in Biochemistry style. the structure file name and the page title. More ambitious students could personalize the file in other ways, such as changing the background. jmol.php

Template file downloaded and modified to use at least five Jmol commands (represented as radio buttons or check boxes) to help readers understand the protein’s structure and function (again configurable by advanced users)

learning. PHP may seem to add an extra complexity to the structure but it actually simplified the process from the student perspective because students did not need to know anything other than very basic HTML text formatting commands to prepare their pages. The PHP structure dynamically created each Web page from the discrete parts submitted by students.

’ DISCUSSION As the goal for this project was to increase student engagement without sacrificing content, students were surveyed after completing the course to assess their perceptions of the experience. Out of 40 students taking the course over two years, 27 (68%) responded to an anonymous SurveyMonkey30 survey request (Figure 2). Students were asked about the value for each component of the project (Figure 3A for responses) and also

about their level of agreement on six statements related to the project goals. These statements are listed in Figure 2 and the responses are plotted in Figure 3B. As can be seen from Figure 3A, most students agreed or strongly agreed that the project was useful in helping master the concepts introduced in lectures. In general, the sequence assignment was rated the lowest. Even though the electronic protein function paper was incorporated into the Web site, students reported the paper by itself to be less useful than when incorporated into a Web site. Students also agreed strongly that the project was a useful learning tool. Figure 3B shows that for each question the median response was 5 or 6. Student disposition toward the course was very positive. We are currently working on building assessments for specific course content areas into future classes. Many new skills were required to successfully complete this project including scientific literature research, protein sequence analysis, protein structure analysis, and Web site design. These skills were taught using a voluntary tutorial program. During these tutorials, students learned the necessary skills by using a standard protein, the transcription factor GAL4 (pdb code: 1d6631). Tutorials worked well to answer global questions while allowing students to work at their own paces. At the onset, a main concern for students was how to learn HTML and Jmol. Surprisingly, whereas all students were comfortable with the Internet, few had actual experience constructing Web sites (at least at the HTML level). Therefore, the template-based Web site was critical to building their comfort with the process. Very little HTML coding, if any, was needed to complete the Web site and even the most anxious students felt accomplished after the final project was submitted. In terms of Jmol, students saw many of its features in the FirstGlance-driven3 protein structure tutorial session. This, along with the simplified coding and several excellent Jmol Web sites,2,3,32,33 facilitated students’ transitions to intermediate Jmol users. Samples of all files used are available in the Supporting Information. 1076

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Figure 2. Survey statements posed to students after completing biochemistry. Respondents were asked to rank their agreement with each statement on a 6-point Likert scale: 1 (strongly disagree) to 6 (strongly agree).

Figure 3. Results from student surveys. Panel A plots students’ assessment of specific assignments when prompted with the question: “I required you to do a research project for the class. I really would like to hear how you feel about the project now that the class is over. Below I have listed several components for the project. How helpful were each of these research project components in mastering particular concepts covered in class?” The average response to the 6-point Likert scale (1, not helpful to 6, very helpful) is shown in parentheses in the legend. Panel B shows students’ agreement with the statements listed in Figure 2. The average response to each prompt is shown in parentheses in the legend.

This research component adds a significant amount of work for students, and therefore, it was weighted heavily in the grading (30% of the final grade). Besides 5 in-class exams and the final, there were no other assignments collected. This project also adds a nontrivial amount of work for instructors. Getting quick feedback to students while they are writing their papers is critical to their success. In our experience, the workload is manageable for classes of about 20 students; more could be managed with a well-trained teaching assistant. The student Web sites needed to be hosted on a server with the PHP module. The Berea College chemistry department has an independent server that was used to host the student Web sites. We set up a “biochemistry” user with access only to the biochemistry directory. The directory structure is explained in the Supporting Information. Within/home/biochemistry/public_html, a directory was set up for class, and within that directory, a folder for each student with a complete set of template files. Another directory was set up to contain the JmolApplet2 (/home/biochemistry/public_html/bin/) and the globally loaded information files (Protein.css, links.php, and contact.php). When students were

ready to begin assembling their Web sites, they were instructed to download a freeware FTP client and given a temporary password to the biochemistry account. Students downloaded the template files to their own computers, modified them, and uploaded them back to the server. After modification, they could quickly reload the page to see the impact of their changes. This instantaneous feedback was very useful to troubleshoot and learn Jmol. All students logged into the same biochemistry account and the password was changed once the final submission deadline passed. Although we had no security problems, a more secure process could be constructed by having windows of time for accessing the server (changing passwords between) or having all files submitted to the teaching assistant or instructor for upload to the server. Another possibility we are pursuing is the construction of a PHP/MySQL-driven Web page into which students could copy-and-paste text into a Web page. This page would save the entries in a database and then dynamically construct the Web sites as they were called. If an instructor is interested in this project but has institutional restrictions on PHP-based Web sites, HTML could be used exclusively with frames to segment the page. 1077

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Journal of Chemical Education The Jmol requirement is harder to circumvent, but no security problems with Jmol have been reported.2 Certainly, such projects should not be undertaken without consulting the computer system administrator or campus information system managers. Another value for this new format is the ease of peer review. One class day toward the end of the term was reserved for peer review. Each student or group was assigned two other student projects to review and required to post their evaluations to a class-wide discussion board. Students were not only interested in each other’s proteins, but they were also interested in how each person or group used Jmol. Final projects ranged from the minimal use of Jmol to quite sophisticated animations and representations of multiple substrates in one binding site. The public peer review process also elevated the quality as each student or group did not want to have the worst Web page. We believe this approach is better than one in which student work is posted to an intranetwork such as a class Moodle or Blackboard site because the student work is globally visible. Students have reported sharing the links to their sites with friends and family, which is not possible with restricted access sites.

’ CONCLUSION Although incorporating Web pages into a chemistry research project may seem to be an additional burden on both faculty and students, we found that students were more motivated and engaged. Because of the simplification of the Web page development, this structure offers easy in-class implementation in introductory biochemistry courses or any chemistry class that heavily relies on molecular structure. Although none of the students involved reported previous experience with HTML, JavaScript, or Jmol, the initial implementation was successful and continues to be used in introductory courses. ’ ASSOCIATED CONTENT

bS

Supporting Information Samples of handouts for tutorial sessions and examples of the required files needed to construct the Web sites. This material is available via the Internet at http://pubs.acs.org.

’ AUTHOR INFORMATION Corresponding Author

*E-mail: [email protected].

’ ACKNOWLEDGMENT We would like to thank Jay Baltisberger for his Unix, HTML, PHP, and Jmol assistance, Jon Saderholm for his assistance with construction and analysis of survey data, Berea College for its support, and Berea College’s biochemistry classes for testing out this new project. ’ REFERENCES (1) ACS Guidelines for Bachelor’s Degree Programs. http://portal. acs.org/portal/PublicWebSite/about/governance/committees/training/ acsapproved/degreeprogram/WPCP_008491 (accessed May 2011). (2) Jmol: An open-source java viewer for chemical structures in 3D. http://jmol.sourceforge.net/ (accessed May 2011). (3) FirstGlance in Jmol. http://molvis.sdsc.edu/fgij/index.htm (accessed May 2011).

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(4) W3 Schools.com HTML Tutorial. http://www.w3schools.com/ html/default.asp (accessed May 2011). (5) PHP: Hypertext Preprocessor. http://www.php.net/ (accessed May 2011). (6) Java, Sun Microsystems, Santa Clara, CA, 2009. http://java. com/en/ (accessed May 2011). (7) Web Style Sheets. http://www.w3.org/Style/ (accessed May 2011). (8) It0 s About Chime. http://www.umass.edu/microbio/chime/ abtchime.htm (accessed May 2011). (9) Cass, M. E.; Rzepa, H. S.; Rzepa, D. R.; Williams, C. K. J. Chem. Educ. 2005, 82, 1736–1740. (10) Introduction to Organic Nomenclature. http://molecularmodels. ca/nomenclature/nom1.htm (accessed May 2011). (11) ChemTube3D—Interactive 3D Organic Reaction Mechanisms. http://www.chemtube3d.com/ (accessed May 2011). (12) Bottomley, S.; Chandler, D.; Morgan, E.; Helmerhorst, E. Biochem. Mol. Biol. Educ. 2006, 34, 343–349. (13) Concepts in Biochemistry—Structure Tutorials. http://www. wiley.com/legacy/college/boyer/0470003790/structure/structure.htm (accessed May 2011). (14) Herraez, A. Biochem. Mol. Biol. Educ. 2006, 34, 255–261. (15) McMahon, B.; Hanson, R. M. J. Appl. Crystallogr. 2008, 41, 811–814. (16) Martz, E. Biopolymers 2009, 92, 76–77. (17) Thompson, S. E.; Sears, D. W. Biochem. Mol. Biol. Educ. 2005, 33, 344–350. (18) Cammer, S. Bioinformatics 2007, 23, 383–384. (19) The Online Macromolecular Museum Exhibits. http://www. callutheran.edu/Academic_Programs/Departments/BioDev/omm/ exhibits.htm (accessed May 2011). (20) Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. Nucleic Acids Res. 2000, 28, 235–242. (21) Scopus, Elsevier B. V., New York, NY, 2009. http://www. scopus.com/home.url (accessed May 2011). (22) Martz, E. Trends Biochem. Sci. 2002, 27, 107–109. (23) National Center for Biotechnology Information Protein Home. http://www.ncbi.nlm.nih.gov/sites/entrez?db=protein (accessed May 2011). (24) VectorNTI. http://www.invitrogen.com/site/us/en/home/ LINNEA-Online-Guides/LINNEA-Communities/Vector-NTI-Community/Vector-NTI.html?CID=fl-bioinformatics (accessed May 2011). (25) Hirokawa, T.; Boon-Chieng, S.; Mitaku, S. Bioinformatics 1998, 14, 378–379. (26) National Center for Biotechnology Information BLAST Home. http://blast.ncbi.nlm.nih.gov/Blast.cgi? CMD=Web&PAGE_TYPE=BlastHome (accessed May 2011). (27) Crosson, S.; Moffat, K. Plant Cell 2002, 14, 1067–1075. (28) LOV Structural Tutorial. http://chemistry.berea.edu/ ~biochemistry/Anthony/LOV/ (accessed May 2011). (29) Landau, M.; Mayrose, I.; Rosenberg, Y.; Glaser, F.; Martz, E.; Pupko, T.; Ben-Tal, N. Nucleic Acids Res. 2005, 33. (30) Survey Monkey. http://www.surveymonkey.com/ (accessed May 2011). (31) Marmorstein, R.; Carey, M.; Ptashne, M.; Harrison, S. C. Nature 1992, 356, 408–414. (32) Jmol interactive scripting documentation. http://chemapps. stolaf.edu/jmol/docs/ (accessed May 2011). (33) An Introduction to Jmol Scripting. http://www.callutheran. edu/Academic_Programs/Departments/BioDev/omm/scripting/ molmast.htm (accessed May 2011).

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