Before he can begin designing a molecule, Li must obtain information about a specific protein target, especially the protein structures. These details come from collaborators who have already mapped a target protein's surface to pinpoint where the hot spots are, for example, through directed mutations or from databases.
Li starts the design process with molecular fragments that come from thousands of existing drugs already on the market. He creates a computer image of those molecules, and then chops them up into tiny pieces and creates a library of substructures to work with typically more than a thousand possibilities.
That is where computational power comes into play.
"To search all of the possibilities of these molecular combinations and narrow them down, we need a massive computer," he said. Li uses two clusters of multiple computers, one in Ohio State's College of Pharmacy and the other in the Ohio Supercomputer Center, to complete the simulations.
The results of this computation create an initial molecular template that can serve as a blueprint for later stages of the drug discovery process. Medicinal chemists can assemble synthetic molecules based on these computer models, which can then be tested for their effectiveness against a given disease condition in a variety of research environments.
Li already has used this technique to identify molecules that bind to known cancer-causing proteins. He said the method can be applied to any protein that is a suspected cause of diseases of any kind, not just cancer.
|Contact: Chenglong Li|
Ohio State University