COLUMBUS, Ohio Scientists here are taking the trial and error out of drug design by using powerful computers to identify molecular structures that have the highest potential to serve as the basis for new medications.
Most drugs are designed to act on proteins that somehow malfunction in ways that lead to damage and disease in the body. The active ingredient in these medicines is typically a single molecule that can interact with a protein to stop its misbehavior.
Finding such a molecule, however, is not easy. It ideally will be shaped and configured in a way that allows it to bind with a protein on what are known as "hot spots" on the protein surface and the more hot spots it binds to, the more potential it has to be therapeutic.
To accomplish this, many drug molecules are composed of units called fragments that are linked through chemical bonds. An ideal drug molecule for a specific protein disease target should be a combination of fragments that fit into each hot spot in the best possible way.
Previous methods to identify these molecules have emphasized searching for fragments that can attach to one hot spot at a time. Finding structures that attach to all of the required hot spots is tedious, time-consuming and error-prone.
Ohio State University researchers, however, have used computer simulations to identify molecular fragments that attach simultaneously to multiple hot spots on proteins. The technique is a new way to tackle the fragment-based design strategy.
"We use the massive computing power available to us to find only the good fragments and link them together," said Chenglong Li, assistant professor of medicinal chemistry and pharmacognosy at Ohio State and senior author of a study detailing this work.
Li likens the molecular fragments to birds flying around in space, looking for food on the landscape: the protein surface. With this technique, he creates computer programs that allow the
|Contact: Chenglong Li|
Ohio State University