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Modeling Hemoglobin: From Protein Folding to Sickle Cell Disease Slide Deck
Students use 3D alpha- and beta-globin models to investigate all four levels of protein structure while connecting molecular details to a real patient story and the genetics of sickle cell disease. Anchored in the case of Victoria Gray, students begin at the organism and organ-system level (symptoms, circulation, red blood cell shape), then zoom in to the cellular and molecular scales to explore how hemoglobin’s structure enables oxygen transport—and how a single amino acid substitution (glutamic acid to valine at position six in beta-globin) can distort red blood cells and impair blood flow. Along the way, they trace the globin backbone from N- to C-terminus, link “bends” in the ribbon to individual amino acids, examine selected sidechains, and classify them as hydrophilic or hydrophobic to explain how polarity, charge, and the hydrophobic effect drive folding into tertiary and quaternary structures and position heme groups for oxygen binding.
Designed primarily for grades 9–12 Biology, Honors Biology, and AP Biology, this activity fits comfortably into one 60–75 minute class period for the core investigation, with an additional 45–60 minutes if you choose to use all extensions and assessments. It pairs especially well with 3DMD’s Amino Acid Starter Kit and Protein Student Modeling resources, giving students a concrete bridge from amino acid properties to full protein models. The slide deck includes student-facing prompts and rich teacher notes, with built-in routines such as Notice–Wonder charts, quiet thinking time, turn-and-talk discussion, digital and physical modeling, and frequent formative checks to surface misconceptions about protein structure, red blood cell function, and genetic disease.
For advanced high school or introductory college courses, optional extensions connect protein structure to gene structure and biotechnology. Students can map the 146–amino-acid beta-globin chain back to its gene with exons and introns, examine carbon monoxide as a competitive inhibitor at the heme site, and discuss how CRISPR-based genome editing has been used clinically to treat sickle cell disease, including in Victoria Gray’s case. These extensions support NGSS performance expectations HS-LS1-1 and HS-LS1-2 (structure and function of proteins), HS-LS3-1 and HS-LS3-2 (inheritance and variation of traits, including the Glu→Val mutation), and highlight crosscutting concepts of Structure and Function, Cause and Effect, and Systems and System Models, making the lesson a strong fit for units on molecular genetics, heredity, human physiology, and biotechnology.
Plan for one model per lab group – students can use either the Beta-Globin Mighty Model, or the Alpha-Globin Mighty Model. When the Sickle Cell mutation is discussed, lab groups can combine, or those with an alpha-globin model can engage with their models and the images in the slide deck. If you have 2 alpha- and 2 beta-globin models, have your students combine them to experience quaternary structure! Amino acid sidechain models are also needed – either from the Amino Acid Starter Kit or print free paper versions.
Slide Decks incorporate all the information an educator needs to run the activity in one file. Slides that are meant for student viewing feature a green top banner. Slides that are meant only for teacher viewing feature a purple top banner and are hidden in slide-show mode. Each student slide will include a prompting icon in the top right corner. These icons on each slide cue your students to the type of activity they will be doing. Student slides provide notes (teaching notes below the slide) with specific information to assist you in facilitating the activity using effective modeling and education practices.
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