SAN FRANCISCO -- In research that could lead to better drug design, a Duke University bioorganic chemist is exploiting the differences between two forms of water to probe how proteins' shapes control the way they bind with other molecules.
Such binding reactions, which occur constantly in watery solutions within our bodies, require removing much of the water in and around the protein's binding site to make room for the binding partner, said Eric Toone, a Duke associate professor of chemistry.
Removing this water provides much of the energy that drives a binding reaction, and determining how much energy this removal provides has previously been impossible, he added in an interview.
Toone, who made his deductions using a supersensitive instrument that can measure 1 millionths of a degree temperature changes, prepared his findings for presentation at the American Chemical Society's national meeting.
Toone's research is supported by the National Institutes of Health, the Camille Dreyfus Foundation and the Alfred P. Sloan Foundation.
Molecular binding events control many biological processes within our bodies, from the activity of enzymes to the signaling that takes place within cells. And blocking these binding events using synthetic molecules is the basis of action of almost all pharmaceutical compounds, Toone said.
Chemical reactions in the body typically unfold when smaller molecules, called "ligands" form temporary combinations, called complexes, with protein molecules at special protein binding sites. Pharmaceutical researchers can elicit biological effects by designing drugs to link up with proteins just as natural ligands do. But in the process the drugs block the natural action of the protein.
Toone said a "holy grail" of pharmaceutical chemistry -- the
so-called "rational design"of drugs -- requires that scientists
know enough about the architecture of proteins to devise
Contact: Monte Basgall