Structure Based Docking in the
Classroom
If you are a
professor interested in teaching virtual screening or a
student wanting to learn how to dock on your own, it can be
done! See below for a full tutorial using the
visualization software ChimeraX and the Vina docking
program. By using these programs, you do not need to
purchase any software and you can use either a Mac or
PC. Note that the instructor will have provide a PDBQT
file for the protein target, or you'll have to create one
yourself using instructions found
here. I
also provide the PDBQT files that I use for my course at the
bottom of this page. As an instructor, I use a docking
assignment in an upper-division medicinal chemistry course
where each student is assigned a crystal structure with a
bound drug, then tasked with docking their own
rationally-designed derivatives of the drug in order to
discover a more potent candidate.
Using ChimeraX
ChimeraX is a freely available molecular graphics
program that we highly recommend. A full tutorial,
including download instructions, can be found here.
You can also find a collection of
useful ChimeraX commands here.
Vina Docking Tutorial with
Webina
A full tutorial using the 1stp crystal
structure of streptavidin and the web browser
Webina can be found here.
This is recommended for beginners and/or those
without a background in line commands or Unix
environments, since the Vina program is run
through the help of a web browser
interface. Ligands must be run one at a
time, so it's best for testing small numbers of
compounds. You'll also need to download
the following files:
Create
a folder on your Desktop called DockingJob (this
is also described in the tutorial). Within
this folder, place the following items:
|
Docking Tutorial with Line
Commands
This is a more
advanced tutorial and requires the user to execute Vina
locally by line command. A script is provided that
can run large numbers of ligands. A full tutorial
using the 1stp crystal structure of streptavidin can be
found here.
You'll also need to download the following items,
depending on your operating system:
Files for Windows Users
Create a
folder on your Desktop called DockingJob (this
is also described in the tutorial). Within
this folder, place the following items:
|
Files for Mac Users
Create a
folder on your Desktop called DockingJob (this
is also described in the tutorial). Within
this folder, place the following items:
|
Instructor Resources
If you are an instructor and want
to incorporate this exercise into your class, feel free to
use my materials free of charge. When I teach docking
the in the classroom, I first have students complete an
assignment where they learn to work with ChimeraX (you can
see an example here).
After grading and returning the ChimeraX assignment, I then
give the students a docking assignment where I ask them to
design novel derivatives of known drugs (example using
Webina here,
and a more advanced example assignment with line commands here). I will
give an individual student the same crystal structure for
both the ChimeraX and the docking assignments. I also
provide students with a drug design example here
demonstrating how to go about making derivatives from a
known compound based on a SAR model.
There are a number of possible structures
you can assign, but I stick to protein structures bound to
drugs since my course is a medicinal chemistry
elective. Below you can find the PDBQT files that I
have prepared if you want to just use my structures (note
that I don't often assign the metalloprotein structures 1rj6
and 2x8z, as Vina gives very low scores for these
compounds).