Small Wonders, Big Universe

Fall 2013

An invisible universe of all possible organic molecules is truly the final frontier—the exploits of the USS Enterprise and her crew notwithstanding—according to Pitt synthetic chemist Peter Wipf, a Distinguished University Professor who collaborates with many Pitt med people. The vast, unmapped chemical no-man’s-land is as compelling to Wipf as outer space is to Captain Kirk. Discovering useful compounds that no one has seen or imagined could very well address humanity’s most vexing problems, from the need for energy sources to treatments for disease.

But new compound discoverers like Wipf face daunting odds. Trying to locate a specific molecule in the vast chemical universe made up of at least 1060 (a novemdecillion) different compounds is akin to the Enterprise making a random warp jump without the benefit of specific coordinates— scientists could end up anywhere. And they do all the time. Finding specific compounds with particular properties is not simple. Enter the Small Molecule Universe Project.

Wipf and colleagues at Duke University have created an algorithm called ACSESS (Algorithm for Chemical Space Exploration with Stochastic Search) that generates a map of molecular space. The algorithm plots all known organic compounds (anything with carbon) within a range of molecular weights. Then it creates a library of novel compounds as researchers feed in parameters. If you want to improve on properties of a known molecule, the algorithm will help you discover related molecules that can be synthesized in the lab. The catch is that you need to know where you are going—and that prospect could turn traditional drug development on its head. Typically, researchers search for new drugs within the relatively small collection of molecules that we already know exists. But by feeding progressive sets of coordinates into this chemical warp drive, says Wipf, scientists can build a custom molecule, bit by bit, to perfectly address the molecular properties of a given problem.