"Each bird can see the landscape individually, and it can sense other birds that inform each other about where the foods are," Li said. "That's how this method works. Each fragment is like a bird finding food on the landscape. And that's how we place the fragments and obtain the best fragment combination for specific protein binding sites."
Li verified that the technique works by comparing a molecular structure he designed to the molecular base of an existing cancer medication that targets a widely understood protein.
"My method reconstructed what pharmaceutical companies have already done," he said. "In the future, we'll apply this technique to protein targets for diseases that remain challenging to treat with currently available therapies."
The research appears online and is scheduled for later print publication in the Journal of Computational Chemistry.
Li said this new computer modeling method of drug design has the potential to complement and increase efficiency of more time-consuming methods like nuclear magnetic resonance and X-ray crystallography. For example, he said, X-ray fragment crystallography can be hard to interpret because of "noise" created by fragments that don't bind well to proteins.
With this new computer simulation technique, called multiple ligand simultaneous docking, Li instructs molecular fragments to interact with each other before the actual experimental trials, removing weak and "noisy" fragments so only the promising ones are left.
"They sense each other's presence through molecular force. They suppress the noise and go exactly where they are supposed to go," he said. "You find the right fragment in the right place, and it's like fitting the right piece into a jigsaw puzzle."
|Contact: Chenglong Li|
Ohio State University