Key Points
- Researchers at St. Jude have created a new computational tool called ColdBrew.
- It solves a major problem in drug discovery, where freezing proteins for study creates inaccurate data about the water molecules around them.
- The tool helps scientists design better drugs by predicting the precise location of water molecules on a protein at normal temperatures.
- This allows drug designers to determine which water molecules a new drug must displace to be effective.
Scientists at St. Jude Children’s Research Hospital have developed a powerful new computer tool called ColdBrew, which could aid in designing more effective drugs. The tool addresses a major, often overlooked problem in drug discovery: how to account for the water that surrounds every protein in the human body. The research was published today in Nature Methods.
Think of it this way: for a drug to work, it often has to push water molecules out of the way to dock onto a protein. However, when scientists study proteins, they typically do so at temperatures close to freezing. This freezing process can distort the data, making it appear as if water is present in places where it wouldn’t normally be at body temperature. Because this data was so unreliable, drug designers often just ignored the water molecules altogether. One of the researchers called them “kind of inconvenient.”
The new ColdBrew tool solves this problem. It examines the data from a frozen protein and predicts the likelihood of a specific water molecule being present at normal, non-frozen temperatures. It essentially provides scientists with a reality check, allowing them to identify which water molecules are truly important and “stuck on” and which are merely artifacts of the freezing process.
To make the tool immediately useful, the St. Jude team has already used ColdBrew to analyze the entire public library of protein structures—that’s over 100,000 structures and 46 million water molecules. They found that drug designers were already unknowingly avoiding these “sticky” water spots. With ColdBrew, they can now do it with much more precision, potentially leading to better and faster drug development.
