With the help of AlphaFold, researchers are designing drugs that are more effective than ever
Karen Akinsanya is President of R&D, Therapeutics, at Schrödinger in New York. She shares her AlphaFold story.
What has always captivated me is the idea that you can go from bench to bedside.
I have worked in academia and drug discovery and development. This means that I have not only studied proteins and genes and figured out how to make a therapeutic molecule against a pathogenic target, but I have also been at a patient’s bedside as they received this new drug.
But the real question is: how can we improve the way we do things? People are still dying every day from cancer and heart disease while we wait for solutions.
I always say that mother nature is thrifty. When you come across a target for a new drug, you often find other potential targets that look like brothers, sisters, and cousins. Each target is a protein on the surface of a cell that the drug binds to, called a receptor. The challenge for people working in drug discovery is to find a drug or molecule that binds one member of that family – the target – and inhibits that family member, but does not inhibit the rest of the family. This is part of where AlphaFold worked so brilliantly for us.
In some cases, AlphaFold – in combination with our own physics-based software that simulates how atoms interact – allows us to begin to simulate not only what members of a family do, but also the behavior of different groups family.
Being able to design a selective drug that only hits a specific target is one of the most important things in drug discovery.
This is particularly important when designing medications for our endocrine hormonal system, which is regulated by the pituitary gland and a number of hormones and messengers that circulate throughout the body.
In our recent work, we have explored ways to design molecules that selectively mimic the actions of natural messengers, particularly those that affect the functioning of our brain. In this case, we focus on the neurotransmitters of many neurological diseases, including schizophrenia and bipolar disorder.
What we found exciting is that using AlphaFold’s predictive structures alongside our structure refinement and drug design software potentially allows us to design a molecule that targets a family member of interest – in this case, a signaling partner in the brain – with exquisite performance. precision. This is something that people have been trying to do for years and has many potential treatment outcomes.
Yet, in the end, it’s only when this drug reaches a real person that we see what the culmination of all this research is. Will this really make a difference?
Ever since James Watson and Francis Crick discovered the double helix structure of DNA, we’ve been trying to better understand the building blocks of how and why our bodies work, and how and why they sometimes deteriorate. As a human race, we ask ourselves: what is the code of life? In terms of drug discovery, AlphaFold is an additional piece of this puzzle. Each of the elements required to design a drug is extremely complex. But putting a few pieces together could accelerate drug discovery in ways never before seen.