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Depression chemistry: part 2

Watch David describe the molecular evolution of our current day antidepressants.
This animation shows us a non-human transport of protein that very usefully binds antidepressant drugs. This protein gives us tantalising clues to the important chemical features these drugs need to act as antidepressants. Let’s introduce here, Fluoxetine, and as we rotate it around, we will show the amino acids that surround the drug. The drug itself fits into a very tight pocket, and we can see, as the amino acids are shown in the green, that they surround our drug, Fluoxetine, which has the Grey carbon atoms.
I can now introduce more antidepressant drugs. The first one I will pull in is sertraline. The second is desvenlafaxine and the last one, clomipramine, all of them antidepressant drugs, and what we can see here is that they occupy the same space. They’re fitting into the same pocket within the protein. Let’s show you some of those important chemical features. First of all, the basic nitrogen atoms with the blue spheres, representing the nitrogen atoms, and we can see that they are in the same region of space. Likewise, the hydrophobic sections of the molecules, which are shown in the orange here, occupy the same region of space.
We will now colour each of the molecules with a different colour. Following this, we’ll put a surface on each molecule to show us their overall shapes, and by combining all those shapes together, we get a picture of the pocket of the protein. So, all of these molecules fit into the same pocket and this overall shape tells us just how big it is and where the common groups lie. Let’s put this into the context of the entire protein. This pocket in the protein lives right in the heart of the protein.
If I put a surface on the protein and now rotate it around, you will see that these molecules bind into a deep cleft, and we see the molecules way down there.
So what we’ve seen here is that these antidepressants bind into the protein, sharing common binding sites for the nitrogen atoms, the hydrophobic groups, and that they occupy the same space, and, potentially, we could use this for the design of new drugs.

Watch David describe the molecular evolution of our current day antidepressants.

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The Science of Medicines

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