Scientists require small molecules -- composed of a few dozen atoms at most -- to serve as foundations for potential drugs or to serve as tools for biomedical research.
The problem is that there are a potential 1023 possibilities -- an astronomical number.
So the National Institutes of Health has funded two Duke theoretical chemistry teams headed by professors David Beratan and Weitao Yang to suggest new schemes to drastically reduce the field of candidates.
The two Duke theory groups plan to collaboratively develop methods to identify subsets of molecules that are the most chemically different from each other. That way, "when experimentalists make hundreds or thousands of candidate molecules in the course of this project they will choose the most diverse set they could possibly make, and thus have the best statistical chance of finding a hit," Beratan says.
The Duke chemists were tapped to participate in one of five NIH Centers of Excellence in Chemical Methodologies and Library Development because of their earlier work under a Defense Advance Research Project Agency (DARPA) "grand challenge" initiative seeking radical techniques to speed searches for promising chemical compounds.
Duke postdoctoral researcher Shahar Keinan was first author of a July report in the journal Organic & Biomolecular Chemistry that incorporated a method developed in Duke's earlier DARPA-funded investigation to search for the optimal quinone molecule for a certain use.
The journal's cover highlighted the selected quinone -- blown up and in primary colors -- superimposed over smaller and drabber background competitors that were weeded out. "Each one of those little molecules in the background is distinct from every other one," Beratan says. "It begins to give you a sense of how vast the molecular possibilities are."