What Do Drug Discovery Models Actually Get Right?

Drug discovery models have gotten better and better at the first job: choosing a molecule that binds a chosen target well. Nworah Ayogu said the work after a bind still has room to grow. The next models have to predict what the body does once a molecule binds, and which unwanted effects come with it.

People often point to companies like Isomorphic and Chai. A target is a molecule in the body, and hitting it changes something. Biological risk is whether the target is the right one. Upregulate it or downregulate it, and the open questions are whether a person gets sleepier, more awake, or loses weight. Off-target effects are the side effects to avoid, including nausea, a higher heart rate, and liver toxicity. The aim is the intended change without the rest. A molecule still has to be made to bind the target, and some molecules are easier to make than others. Undruggable means the pocket is small. The shapes are three-dimensional, so Nworah Ayogu said the molecule itself may move when part of it is bound and let something else bind, which is why people talk about hidden pockets. A model has to predict the shape in real time and how the shape changes over time.

Step one is the best thing to make so it binds. Step two is what happens after the bind. Step three is the unwanted effects. Binding well is the step the field has improved.