COLLEGE STATION, Nov. 6, 2007 Fitting a key into a lock may seem like a simple task, but researchers at Texas A&M University are using a method that involves testing thousands of keys to unlock the functions of enzymes, and their findings could open the door for new targets for drug designs.
Texas A&M researcher Frank Raushel is part of a team of scientists who modified a technique called molecular docking to predict which molecule, called a substrate, triggers an enzyme into action, enabling them to decipher an enzymes function based on its structure alone.
The teams paper was published in the journal Nature.
Most biological processes depend on enzymes, which are proteins that speed up chemical reactions, but the function of many enzymes remains a mystery.
There are thousands of molecules that could be substrates [for a specific enzyme], and it would take too long to physically test them all, Raushel said. So we decided there was a need for a new method to determine the function of enzymes.
The team started with the three-dimensional X-ray structure of an enzyme and then used a computer to try to fit different smaller molecules into the active site of the enzyme like pieces in a puzzle.
Each enzyme has a specific size and shape, Raushel said, and you can use a computer to take small molecules and fit them into the active site of an enzyme one by one and score them on how well they fit. Its more or less like fitting a key into a lock, but a lot more difficult since both the enzyme and the substrate are conformationally flexible.
After the computer scores the molecules on how well they fit the enzyme, it ranks their order, and the researchers can then use the prioritized list to decide which molecules to physically test.
As far as we know, this is the first time anybody has used molecular docking to predict the function of an enzyme, Raushel said. And it was verified by both experiment an
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Texas A&M University