Enzyme Inhibitor Drug Design Activity by chemteacher628

Last crawled date: 3 years ago

This printable "enzyme" with multiple target sites is designed to teach students the basics of small molecule drug design as well as serve as an introduction to using basic CAD design software to build 3D-printable objects. The enzyme has multiple active sites and surface binding sites. Students will download the STL file into a program such as Tinkercad and will use the CAD software to design "molecules" that could fit into the target sites and block the enzyme from binding to its normal small molecules. The model includes sites for competitive and non-competitive inhibition of the enzyme. One of the noncompetitive sites, when a "drug molecule" binds to it, closes off an active site (see pictures) to demonstrate how allosteric binding can change the structure of the enzyme.
Once students design molecules that can inhibit the protein, the models can be printed and tested with the the printed enzyme. Successful small molecule drugs should fit snugly into the target sites. In this process, the students will also learn strategies for successful printing and how/when to use infill, rafts, and supports.
Once printed, students can compare the different solutions to the same target sites, leading to a discussion of how many drugs for the same problem bind to the same site but have slightly different structures (i.e. Claritin and Zyrtec for allergies). The advantages and disadvantages of these slight differences (such as half-life in the body and side-effects) can be discussed.
Lastly, students can connect their designs to molecular geometry by trying to recreate their drug designs using the basic shapes that molecules can form. This will then lead to a discussion of the real-world process of drug design.