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Electron Location, Location, Location: Understanding Biological Interactions

Introductory Biology courses typically introduce the structure and function of biomolecules such as proteins and nucleic acids. To understand biomolecules fully, students require knowledge of fundamental chemistry concepts such as covalent bonding, intermolecular interactions and hydrophilicity/hydrophobicity (1). Students enter our large (>400 student) course with a notoriously limited conceptual grasp of basic chemistry principles. Our lesson is an activity designed on the principles of POGIL (Process Oriented Guided Inquiry Learning). In 50 minutes, students build their own definitions of the following: polar vs. non-polar covalent bonds, hydrophilicity/hydrophobicity and the nature of hydrogen bonding based simply on the relative electronegativities of oxygen, nitrogen, carbon and hydrogen. We find that this exercise improves students’ understanding of these chemical concepts. Since adopting this activity, students have been better able to understand biomolecular structures and predict interactions between molecules.

Primary image: Hydrogen Bond. Possible hydrogen bond interaction that can form between two simple organic molecules.

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Using Open-Source Bioinformatics and Visualization Tools to Explore the Structure and Function of SARS-CoV-2 Spike Protein

The relationship between protein structure and function is a foundational concept in undergraduate biochemistry. We find this theme is best presented with assignments that encourage exploration and analysis. Here, we share a series of four assignments that use open-source, online molecular visualization and bioinformatics tools to examine the interaction between the SARS-CoV-2 spike protein and the ACE2 receptor. The interaction between these two proteins initiates SARS-CoV-2 infection of human host cells and is the cause of COVID-19. In assignment I, students identify sequences with homology to the SARS-CoV-2 spike protein and use them to build a primary sequence alignment. Students make connections to a linked primary research article as an example of how scientists use molecular and phylogenetic analysis to explore the origins of a novel virus. Assignments II through IV teach students to use an online molecular visualization tool for analysis of secondary, tertiary, and quaternary structure. Emphasis is placed on identification of noncovalent interactions that stabilize the SARS-CoV-2 spike protein and mediate its interaction with ACE2. We assigned this project to upper-level undergraduate biochemistry students at a public university and liberal arts college. Students in our courses completed the project as individual homework assignments. However, we can easily envision implementation of this project during multiple in-class sessions or in a biochemistry laboratory using in-person or remote learning. We share this project as a resource for instructors who aim to teach protein structure and function using inquiry-based molecular visualization activities.

Primary image: Exploration of SARS-CoV-2 spike protein: student generated data from assignments I - IV. Includes examples of figures submitted by students, including a sequence alignment and representations of 3D protein structure generated using UCSF Chimera. The primary image includes student generated data and a cartoon from Pixabay, an online repository of copyright free art. 

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Macromolecular math

This worksheet was developed for use in an introductory biology course to review the chemical bonds and structure of biological macromolecules. A nutritional label is provided to illustrate that we consume macromolecules in our foods.

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