below in the Assessment section). These exercises may be appropriate
at the high school level, particularly in an AP Biology course, and the
educational standards potentially addressed at this level are shown in
Students collect protein structure data from an online database, visualize the structure, and collect data on structural features consistent
with binding of small molecules. They also analyze the protein structure, and known ligands, to inform the process of designing a novel
ligand, a potential therapeutic drug.
In our implementation, we have worked with 15–25 students and
one instructor. A teaching assistant will be necessary if the class is
larger. We recommend that these exercises be conducted over
four class periods (or two labs) or, alternatively, three class periods and one lab, preceded by a homework assignment and in-class discussion for students divided into groups of two to four.
Table 2 lists the online databases and computer programs we recommend using in lessons 1–4. The Supplemental Material available with the online version of this article includes comments
and technical tips on using these resources, as well as suggestions
for written work and worksheets for the students to turn in after
completing their analysis.
Table 1. High school educational standards
potentially addressed by these exercises.
Next Generation Science Standards
HS-LS1-2 Develop and use a model to illustrate the
hierarchical organization of interacting systems
that provide specific functions within
AP Biology Learning Objectives
4.1 The student is able to explain the connection
between the sequence and the
subcomponents of a biological polymer and its
4.2 The student is able to refine representations
and models to explain how the
subcomponents of a biological polymer and
their sequence determine the properties of
4.3 The student is able to use models to predict
and justify that changes in the subcomponents
of a biological polymer affect the functionality
of the molecule.
4.9 The student is able to predict the effects of a
change in a component(s) of a biological
system on the functionality of an organism(s).
Table 2. Databases and computer programs that are the easiest to use and most effective for lessons 1–4.
Computer Resource Applications & Use in the Lesson Plan
Therapeutic Target Databasea Drugs and targets searchable by disease (lessons 1 and 3) https://db.idrblab.org/ttd/
Protein Data Bank (PDB)b Protein structures (lessons 1–4) https://www.rcsb.org/
Free program VMDc To visualize and analyze protein structures (lessons 2–4) http://www.ks.uiuc.edu/Research/vmd/
DogSiteScorer serverd To identify cavities in the protein surface, and to calculate their properties and potential for
druggability (lesson 3) https://proteins.plus/
ZINC databasee Known ligands and drugs (lessons 3 and 4) http://zinc.docking.org/ http://zinc15.docking.org/
Online server ProDrgf To create files containing three-dimensional structures of known and novel ligands (lessons 3
and 4) http://davapc1.bioch.dundee.ac.uk/cgi-bin/prodrg
Online server One-Click
To create files containing spatial coordinates of known and novel ligands (lessons 3 and 4) and
to run docking simulations (lesson 4) https://mcule.com/apps/1-click-docking/
Free program Avogadrog To create and visualize 3D structure files for ligands (lessons 3 and 4) https://avogadro.cc/
Online server SwissDockh To run docking simulations (lesson 4) http://swissdock.ch/
Online Docking Serveri To run docking simulations (lesson 4) https://www.dockingserver.com/web/gettingstarted/
aLi et al. (2018).
bAdditional tools are available therein: Protein Workshop and Ligand Explorer, and “Molecule of the Month” library http://pdb101.rcsb.org/motm/motm-by-title.
cHumphrey et al. (1996). VMD tutorial (most relevant sections are “Introduction” and “Working with a Single Molecule”) is available at http://www.ks.uiuc.edu/
dVolkamer et al. (2012).
eIrwin & Shoichet (2005), Sterling & Irwin (2015).
fSchüttelkopf & van Aalten (2004).
gHanwell et al. (2012).
hGrosdidier et al. (2011).
iBikadi & Hazai (2009).