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Using Small Molecules to Modulate a Protein

More About Using a Small Molecule to Modulate a Protein

Small molecules associate with, or bind to, a protein in specific ways. In some cases they modulate the protein’s function by inactivating it. In this animation, a small molecule (in gold) binds to the protein calmodulin (in blue). Calmodulin is a protein that is involved in calcium regulation in a cell and has many important roles in cellular function. The cleft in the protein is an important site that allows it to interact with other molecules. The small molecule binds to this cleft and occupies the site, causing the protein to undergo a conformational change and become inactivated.

Protein Binding Background

In order to understand life’s processes, it is useful to perturb the process and observe what happens.

In genetics, a gene’s functions are investigated by using mutations that disrupt their normal function. Chemical genetics is an analogous approach that investigates the functions of the genes by using small molecules to perturb the proteins—which are encoded by the genes—directly.

In genetics, some mutations result in loss of function, while others result in a gain of function. In chemical genetics, analogous protein perturbations exist that inactivate a protein (loss of function) or super-activate a protein (gain of function).

A Small Molecule Modulates the Function of a Protein

Small molecules associate or bind with a protein forming what can be thought of as a new protein. In the case shown in this animation a small molecule fits into a cleft in the protein. The blue protein, calmodulin, has several important roles in cellular function. The cleft in the shape of the protein allows it to perform many of these functions. When the gold colored small molecule binds with calmodulin it occupies this cleft and thus inactivates the protein.

Protein Binding 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.

  1. Use the animations to make abstract scientific ideas visible and concrete.

  2. Explain important scientific principles through the animations. For example, the biological clocks animations can be used to demonstrate the fundamentals of transcription and translation.

  3. 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.

  4. 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.

  5. Incorporate the animations into Web-based learning modules that you create to supplement your classroom curricula.

  6. Encourage students to incorporate the animations into their own Web-based projects.


HHMI's 2002 Holiday Lectures on Science "Scanning Life's Matrix: Genes, Proteins and Small Molecules"

Protein Binding Credits

Director: Dennis Liu, Ph.D.

Scientific Direction: Stuart L. Schreiber, Ph.D.

Scientific Content: Satoshi Amagai, Ph.D.

Animator: Eric Keller

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