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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Hemoglobin bioinformatics

This is an introduction to bioinformatics using hemoglobin as an example. The worksheets introduce students to resources to explore the DNA, RNA and polypeptide linear structure with a brief introduction to the quaternary structure of hemoglobin.

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Mol* Adaptation: Case of Severe Insulin Resistance

This is an adaptation using Mol* on the original case written. This case focuses on understanding how a mutation in a cell signalling protein (a kinase) can prevent insulin function and lead to diabetes.

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Waking up Anna - Adaptations and Conversion to Mol*

This case focuses on understanding the molecular basis of Anna's sleeping disorder and its treatment. The adaptations addressed question clarity and reformatting to use Mol*.

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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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Understanding COVID-19 Biology to Design a Vaccine

This multi-part case study introduces the reader to the SARS-CoV-2 virus, replication, and treatment. Additional worksheets introduce students to bioinformatics tools of 3-D protein visualization and BLAST searches.

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Yeti or not: Do they exist?

Through this 4-part bioinformatics case study, students will be led through the forensic analysis of putative Yeti artifacts based on published findings.

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Exploring HIV Evolution

In this activity you will study aspects of sequence evolution by working with a set of HIV sequence data from 15 different subjects (Markham, et al., 1998). You will first learn about the dataset, then study the possible sources of HIV for these...

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DNA Subway Learning Resources

DNA Subway is a NIBLSE Recommended resource. This is a collection of learning resources associated with DNA Subway.

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RNAseq data analysis using Galaxy

This is a bioinformatics exercise intended for use in a computer lab setting with life science majors.

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Using DNA Subway to Analyze Sequence Relationships

This is a bioinformatics exercise using the DNA Subway Blue Line, a user-friendly pipeline of bioinformatics tools, to analyze a collection of mosquito DNA bar-code sequences.

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Bioinformatics: An Interactive Introduction to NCBI

Modules showing how the NCBI database classifies and organizes information on DNA sequences, evolutionary relationships, and scientific publications. And a module working to identify a nucleotide sequence from an insect endosymbiont by using BLAST

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Infectious Chocolate Joy with a Side of Poissonian Statistics: An activity connecting life science students with subtle physics concepts

Lesson on what it means for biological processes to be Poissonian, published in CourseSource

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Teaching RNAseq at Undergraduate Institutions: A tutorial and R package from the Genome Consortium for Active Teaching

This lesson plan was created to teach RNAseq analysis as a part of GCAT-SEEK network. It is provided here, both in finished form and with the modifiable source code, to allow flexible adaptation to various classroom settings, published in...

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Homologous chromosomes? Exploring human sex chromosomes, sex determination and sex reversal using bioinformatics approaches

In this four- part guided activity, students will learn about the structure and function of human autosomal and sex chromosomes, view and interpret gene maps, and gain familiarity with basic bioinformatics resources and data through use of the...

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Ethics in synthetic genomics

This is an ethical reflection for students on an issue in genome engineering and the synthesis of potentially infectious viruses. The case study asks students to reflect on material in the linked article. Also included is the grading rubric.

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Mendelian Genetics, Probability, Pedigree, and Chi-Squared Statistics

A lesson that requires students to work through a series of questions pertaining to the genetics of sickle cell disease and its relationship to malaria.

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