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To help undergraduate biochemistry students gain deeper insights into the intricate relationships between protein structures and their biological functions, an instructional website (tutor.lscf.ucsb.edu/instdev/sears/biochemistry) has been developed at the University of California, Santa Barbara with various hands-on, inquiry-based learning exercises that are designed to challenge the critical thinking skills of students and, at the same time, evoke the scientific processes of data discovery, data analysis, inference making, and hypothesis testing. The website stages various activities so that students are exposed gradually to increasingly more complex structural and functional concepts over a 10-week period. For example, students begin their discovery of protein structure first by analyzing Chime-rendered images of standard and nonstandard amino acid structures, then simple peptides, and finally complex protein and enzyme structures. Likewise, students begin their discovery of protein functional data first by analyzing interactive Excel charts displaying data for simple monovalent ligand binding systems (e.g. buffers), then multivalent ligand binding systems with non-interacting or interacting binding sites (e.g. hemoglobin), and finally enzyme kinetic reactions in the absence or presence of inhibitors. To practice the process of making rational connections between structural and functional data, students regularly answer questions of a scientific nature on self-guided tutorials, self-grading practice quizzes, and graded examinations. For example, students might be asked to formulate or select a hypothesis about the properties of the microenvironment surrounding an ionizable group in a protein structure and then draw inferences about pK shifts that might be observed for that group under various experimental conditions; students might also be asked to predict changes in ligand binding data based on structural alterations or alterations in the microenvironment surrounding a ligand binding site.

Almost all of the learning exercises at the instructional website have been created with standard, off-the-shelf programs or multimedia-based software tools, but a few customizations or software enhancements have been adopted to improve the interactive interface with the student. One enhancement, for example, greatly improves structure analysis using the popular Chime web browser plug-in; most web pages displaying Chime-rendered images include JavaScript-encoded “command entry” and “message recall” boxes (tutor.lscf.ucsb.edu/instdev/sears/biochemistry/tw-enz/crbncanhydrase/carbonicanhydrasef.htm/), which enable students to employ a full range of RasMol commands for structure analysis including the default set of commands found in the Chime popup window. A second enhancement facilitates function analysis greatly with Excel (tutor.lscf.ucsb.edu/instdev/sears/biochemistry/sprdshts/hb-mb01-p.xls) or Microsoft Office Web Component (MSOWC) data charts (tutor.lscf.ucsb.edu/instdev/sears/biochemistry/charts/phsat.hta); the interactivity of these data charts has been enhanced by adding adjustable buttons (or slider bars) that allow students to vary constants or data values systematically and interactively during analysis. A third enhancement involves the addition of some relatively simple Visual Basic (VB) code to active server page (ASP) practice quizzes that effectively makes them self-grading tests allowing students to gain instant feedback on their question responses (tutor.lscf.ucsb.edu/instdev/sears/biochemistry/practicequizzes/prqz21/prqz21f.htm.)

Because it is essential to evaluate this highly interactive learning environment to help determine whether the critical thinking skills of students are actually engaged and improved by the multimedia exercises, an ongoing longitudinal assessment has been initiated where student performance is evaluated at three stages, at the start of instruction, 10 weeks later when instruction ends, and four months after the end of instruction. Preliminary results indicate that although students initially have little skill in analyzing protein structure/function relationships, they gain the necessary computer and logic skills to connect important structure/function concepts by the end of instruction, and they also retain these skills (at somewhat diminished capacity) long after instruction is over.