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Anne-Frances Miller
Computing the Chemistry of Vitamins

by Jeff Worley & Robin Roenker

Some two dozen vitamins are known to be essential for good health, serving as 'spark plugs' for almost half of our cells' enzyme engines. Thus, a large fraction of the more than 1,000 reactions taking place in an average cell depends on the chemical properties of vitamins. Anne-Frances Miller, an associate professor of chemistry and biochemistry, is working to understand how vitamins make possible the demanding chemical reactions that are essential to life, and why so few vitamins are able to do this job, given the thousands of different reactions that occur in cells.

Photo of Anne-Frances MillerMiller's research group uses the UK supercomputer and software that applies quantum theory to compute properties of large molecules. These computations can predict how the vitamin molecules work through metabolic processes, especially those involving vitamin derivatives called flavin enzymes. These enzymes allow for a kind of controlled burn, in which the fatty acids are oxidized, allowing the energy released to be captured for use by the body.

"Flavin enzymes play many crucial roles in human metabolism," says Miller. "Deficiency with regard to one of the flavoenzymes essential for fatty acid metabolism has been implicated as a possible cause of sudden infant death syndrome."

Miller and her research team are working to understand how the same molecule can do different biochemical jobs when bound to different proteins, thus allowing cells to use the same vitamin for a variety of different jobs.

These large molecules provide a challenge to the quantum theory software used by Miller's group. Team member Joseph Walsh was able to fine-tune these computations so that theory matched experiment. These calculations would have taken too long had the Miller group not had access to the supercomputing facilities at UK. Having validated the computations, Walsh was able to begin assessing the effects on flavin electronics of hydrogen bonds, local charge and bending of the flavin—all of which are found in protein-active sites and may serve to shape the flavin reactivity. Thus, the Miller group is on its way to determining whether the different reactivities displayed by the same vitamin, in different proteins, can be explained on the basis of electronic differences produced by interactions between the protein and the flavin.

About Anne-Frances Miller

Anne-Frances Miller began her scientific training in molecular genetics and earned degrees in physics and chemistry. She did postdoctoral work at M.I.T. and Brandeis University before joining the faculty of Johns Hopkins University. She came to the University of Kentucky in 1999 and is a member of the departments of chemistry, and molecular and cellular biochemistry.