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“This could accelerate drug discovery in a way that we’ve never seen before”

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“This could accelerate drug discovery in a way that we’ve never seen before”

Karen Akinsanya, President of R&D at Schrödinger in New York, is paving the way to revolutionary drug discovery

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What has always captivated me is the idea that you can go from the bench to the bedside.

Having worked in both academia and drug discovery and development, I’ve been able to not just study a protein or a gene and understand how to make a molecule against a target, but actually be at the bedside of a patient as they're being dosed with the new medicine.

But the real question is, how can we improve the way we do that? People are still dying of cancer and heart disease every single day while they wait for us to find solutions.

I always say that mother nature is thrifty. When you come across a target for a new drug, you often find that the receptors – proteins that bind to the drug – are part of a family. Looking for one target means coming across other targets that are like brothers and sisters and cousins. Basically, many parts of protein structures that determine how proteins fold are reused. The challenge for people working in drug discovery is finding a drug or molecule that binds one member of that family and inhibits that family member, but doesn’t inhibit the rest of the family. In part, this is where AlphaFold has worked so brilliantly for us.

In some cases AlphaFold – in combination with our own physics-based software that simulates how atoms interact – is enabling us to begin to simulate not just what single family members are doing, but how different family groups are behaving.

As a human race we’re asking: What is the code for life?

Being able to design a selective drug that just hits one target rather than many is one of the most important things in drug discovery.

One space where this is important is when designing drugs for our endocrine hormone system, which is regulated by the pituitary gland and a number of hormones and messengers that circulate in the body.

As part of our recent work we've been looking at ways we could design molecules that selectively replicate the actions of natural messengers, in particular those that affect how our brain functions. In this case we're focused on neurotransmitters for many neurological diseases, including conditions like schizophrenia and bipolar disorder.

What we've found exciting is that using predictive structures from AlphaFold alongside our structure refinement and drug design software potentially allows you to design a molecule that targets a family member of interest – in this case a signalling partner in the brain – with exquisite accuracy. This is something that people have been trying to do for years and has a whole host of potential outcomes for treatment.

Still, at the end of the day, it's not until you've been able to see what happens when you put a proposed medicine into a human subject to see what exactly the culmination of all of that research is – and find out: is it actually going to make a difference?

If we go all the way back to Watson and Crick, essentially we’ve been trying to get closer to the building blocks of how and why our bodies work, or how and why they sometimes go wrong. As a human race we’re asking: what’s the code for life? In terms of drug discovery, AlphaFold is one additional piece of that puzzle. Each of the pieces needed for drug design is extremely complex. But putting a few of the pieces together could accelerate drug discovery in a way that I don’t think we’ve seen ever before.