Every now and then I’ll read that drug X was originally created searching for a cure to disease A, but then they find out its a cure for B instead. How do scientists set out to design a chemical that does specific things? And is it just by chance they discover that it helps with, say, erectile dysfunction and market it that way? Especially when the addition of one atom can seemingly vastly change molecule properties.
In: Chemistry
The current top answer here said: “The way a drug works is that compounds in the drugs bond with or block other things in the body from bonding with cells in your body.” That’s true.
But the way things bond with one another is based on their physical shape, the physical arrangement of their atoms, as well the electrical charges on the surface of those shapes.
So we can design drugs deliberately by taking what we know about their shapes, and comparing it to the shapes of important biochemicals in our bodies.
So let’s say you want to design a drug that blocks covid from binding to the ACE2 receptor, so that we can prevent it covid from ever getting inside of our cells.
* First you need to know the shape of the receptor. For covid, we know that the receptor is called ACE2. We do already know its shape.
* Then you need to know how covid binds to ACE2. You need to know which locations on the surface of the receptor are important for covid binding. (I’m pretty sure we know that.)
* And then comes the hard step: figuring out what molecule has the right shape, as well as the right electrical charge, to bind to ACE2 in a way that prevents covid from binding.
* There is a certain amount of guesswork involved here, but it’s not all guesswork. You can do a lot of computer simulations of molecule shapes to figure out that they have very low odds of binding to ACE2. This helps you focus on experimental tests that are more likely to work.
* And you can also do your initial steps using proteins instead of living systems. You can check whether your drug candidate binds to the protein at all, and if it doesn’t, well, then it probably won’t in our bodies either.
And even if you do figure out a drug candidate, there’s ***lots*** of other steps that come after. You have to figure out a way to deliver this molecule to the cell; it’s not helpful to take a pill if the drug stays in your stomach and doesn’t get to your cells. The molecule needs to bind specifically: the shape has to bind to ACE2, but not bind to everything else (otherwise it’d have off-target effects). If the molecule binds to ACE2, it shouldn’t disrupt its normal functions.
But that’s how drug design is done using rational planning. It’s not all guesswork, it’s looking at the ability to chemically bind to one another, based on the shapes of the molecules.
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