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More About DOS Matrix
Generating thousands of novel small molecules to use in experiments, such as the one described in the furrowstatin animation, is becoming an increasingly easier process for scientists, thanks to advances in technology and techniques like diversity-oriented synthesis (DOS).
In DOS, many different small molecular building blocks are combined with each other in all combinations. Many thousands of novel molecules can be created in a relatively few number of reactions. This animation demonstrates DOS by displaying possible combinations of building blocks in a matrix. At its simplest is a 2 X 2 matrix. In this reaction, two related building block molecules are arranged on one axis, one shown in blue and its related cousin in white. Another two molecules are likewise arranged on the other axis, one shown in orange, and its cousin in white. The reaction combines them, forming four new compounds – orange-blue, orange-white, blue-white, and white-white. The process can be taken another step by adding another building block, shown in red, and expanding the matrix by adding a third axis. This step adds four new compounds – red-orange-blue, red-orange-white, red-blue-white, and red-white-white. In total we now have eight new compounds.
When we add a cousin of the red molecule (above the red molecule, shown in white) we now get 12 compounds. Instead of using only two related molecules on each axis of the matrix, we can use more than 40. Such a matrix would generate thousands of new molecules. In this example, which is a matrix of 45 X 45 X 44, over 88,400 new molecules were generated.
DOS Matrix Background
Traditional methods of synthesizing molecules are known as target-oriented synthesis. The aim is to synthesize a specific molecule that has been found in nature or that was designed theoretically. The approach requires a thorough knowledge of many types of chemical reactions, is time-consuming and complicated, and is not always successful.
An alternative approach is diversity-oriented synthesis (DOS). In DOS, many novel molecules are synthesized by combining many different small molecular “building blocks” in all permutations. Having generated many thousands of different molecules, they can then be tested to see if they have useful properties by different screening procedures. (See other animations on screening.)
One advantage of diversity-oriented synthesis is increased throughput. Thanks to advances in computer science, robotics, and chemistry, one researcher working in a lab can generate over 88,000 novel small molecules in a matter of months.
For additional information go to the video clip on Diversity Oriented Synthesis in the Video Clips section.
Resources
HHMI's 2002 Holiday Lectures on Science "Scanning Life's Matrix: Genes, Proteins and Small Molecules"
DOS Matrix Teaching Tips
The animations in this section have a wide variety of classroom applications. Use the tips below to get started but look for more specific teaching tips in the near future. Please tell us how you are using the animations in your classroom by sending e-mail to biointeractive@hhmi.org.
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Use the animations to make abstract scientific ideas visible and concrete.
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Explain important scientific principles through the animations. For example, the biological clocks animations can be used to demonstrate the fundamentals of transcription and translation.
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Make sure that students learn the material by repeating sections of the animations as often as you think necessary to reinforce underlying scientific principles. You can start, restart, and play back sections of the animations.
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Urge students to use the animations in accordance with their own learning styles. Students who are more visually oriented can watch the animations first and read the text later, while others might prefer to read the explanations first and then view the graphics.
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Incorporate the animations into Web-based learning modules that you create to supplement your classroom curricula.
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Encourage students to incorporate the animations into their own Web-based projects.
DOS Matrix Credits
Director: Dennis Liu, Ph.D.
Scientific Direction: Stuart L. Schreiber, Ph.D.
Scientific Content: Satoshi Amagai, Ph.D.
Animator: Chris Vargas
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