Molecular Docking Simulation as a Driver of Hypothesis Formation in an Undergraduate Biochemistry Lab Course
Mentor:Blake Gillespie, Associate Professor of Chemistry, California State University Channel Islands
Enzyme inhibition is a staple of the undergraduate biochemistry lab curriculum. By incorporating a preliminary docking simulation, students are able to augment what is often a ‘canned’ exercise by building in a hypothesis-driven component. Students rank potential inhibitors of Gallus gallus Lactate Dehydrogenase A (LDH-A) by docking a small set of target molecules into a known LDH-A structure using a widely available molecular graphics software package, ICM. The small molecule ligand that yields the highest docking score is predicted to be the most effective competitive inhibitor, while the lowest score is predicted to be the least effective. These theoretical rankings are then tested empirically in the laboratory section of the course through spectrophotometric assay. While positive results support and augment the course’s learning objectives, unexpected results are often also ‘teachable’, revealing misconceptions about the potential competitive inhibitors, and the limitations of the scoring criteria. Though the presented work focuses on a single enzyme system, the method may be applied to many instructional laboratory targets.