Enzyme Inhibitor Drug Design Activity

thingiverse

This printable "enzyme" with multiple target sites is crafted to teach students basic small molecule drug design fundamentals while introducing them to using CAD software to build 3D-printable objects. The enzyme has multiple active and surface binding sites, allowing students to create molecules that could fit into the target sites and block the normal binding process. Students will download an STL file from Tinkercad or a similar program and use CAD design skills to build "molecules" that can inhibit the enzyme's activity at competitive and non-competitive inhibition sites. One of the non-competitive sites will close off an active site when bound by a "drug molecule," demonstrating how allosteric binding changes the enzyme's structure. Upon completing their designs, students can print and test the enzyme models with successful small molecule drugs fitting snugly into target sites. This process helps students learn effective printing strategies and infill techniques, understanding how many real-world drugs share similar structures for targeting the same site (Claritin and Zyrtec). As they continue, students will analyze molecular geometry by recreating their designs using basic shapes molecules can form, ultimately leading to a discussion of real-world drug design. Print settings: Printer: Da Vinci Jr. Rafts: Yes Supports: Yes Notes: Rafts and supports are necessary for the non-competitive file; no additional supports or rafts required for the enzyme itself. After assembly, students should place the non-competitive piece in the active site's side closest to the bottom. The rectangular part fits snugly into the enzyme's sidewall, allowing it to close off the site when a "drug molecule" binds to the stalk. (See pictures below) Assembly steps: Inserting the non-competitive piece into the enzyme. The piece snaps into the enzyme's sidewall. This blockage occurs as the bound "drug molecule" pushes against the piece's stalk, blocking active site activity. Background: Pharmaceutical chemistry sparks student interest in molecular biology and proteins. This lesson helps students understand inhibitors, scientists' designs to fit molecules within target sites on proteins. Preparation: Familiarity with enzymes, active sites, competitive and non-competitive inhibition basics is expected. A basic understanding of protein structure's significance is also assumed. Optionally, introduce students to using CAD software like Tinkercad or 123D Design; the activity can be used as an introduction. Objectives: * Explain the difference between competitive and non-competitive inhibitors. * Describe small molecule drugs designed for inhibition. * Demonstrate designing shapes in CAD programs. * Connect molecular geometry to enzyme target site shapes. * Explain real-world drug design processes. After introducing enzymes, active sites, and inhibitor concepts (using real-world examples like allergy medications), present the drug design activity. Have students download and open an STL file in a CAD program, using software like Tinkercad or 123D Design to build small molecule drugs for various enzyme target sites. Allow students to assist you with necessary techniques as needed. Guide them on how 3D printers work, printing their designs while instructing the optimal use of slicing programs to minimize material usage and enhance quality.