Other tools to visualize the complex structures are Protein
Workshop and Ligand Explorer (Figure 4 bottom left); standalone
Java-based viewers available from the PDB Summary page; or a separate program, VMD (Humphrey et al., 1996). To use VMD most
effectively, we recommend that students download structure files
directly from the PDB (in PDB format; see Figure 4, top right,
“Download Files”) and complete the program tutorial to learn the
basic functions (see Table 2 footnotes). In our experience, learning
the basic operations takes about 15 minutes with instruction and
one to two hours if students work independently through the first
part of the tutorial (“Single Molecule”). Learning VMD is strongly
recommended for highly motivated students or students who will
work on an inquiry-based, longer-term project.
Lesson 3: Ligand Design
We recommend that students complete a homework assignment
before lesson 3 that includes online registrations for servers or
download and installations for the locally run programs to ensure
they complete lesson 3 within 50 minutes. The homework can also
include short practice with molecular editors such as ProDrg or
Avogadro (Table 2).
After completion of lesson 2, students have sufficient background in protein structure, protein involvement in disease, and
the concept of a small drug molecule binding to its protein target.
The goals of lesson 3 are (1) to choose their own target disease and
target protein for rational drug design and (2) to design novel or
modified ligand molecules. The easiest tool to search for a target
or target-drug pair is the Therapeutic Target Database (Table 2),
which students can query by disease, by target, or by drug. Students should note the results of their searches, including search criteria, database hits, and their final selections. They can also be
asked to write a short explanation of why they selected a particular
disease/drug and a summary of information provided by the database for this disease/drug. Table 3 can also be used to initiate the
Figure 4. Protein Data Bank summary page for cyclooxygenase (PDB ID 1PTH).
Figure 5. Example of the Ligand View program output that
shows the protein residues forming interactions with the
bound ligand.
