Bridging the divide: A tale of the merger of computational chemistry and structural biology in enzyme design

The 1965 Westheimer Report suggested "the need for breaking down the barriers between biol. and chem. departments in universities, and for broader training of biologists in chem. and of chemists in biol.". Moreover, Edward Tatum, who shared the 1958 Nobel Prize in Physiol. or Medicine with George Beadle, is quoted as saying "If these [educational] goals can be met, I would predict that within a few decades the structural requirements for many enzyme activities will be clearly understood, a no. of synthetic enzymes will probably be available, either identical to, or even improvements on, the natural enzymes. ... These advances will depend on the availability of investigators trained broadly both in biol. and in chem.". Tatum's prediction that enzymes, and more generally proteins, can be designed is currently being realized by investigators that bridge the divide between the chem. and biol. sciences. This talk will focus on the history of the development of computational protein design from its origins in computational chem. through the design of enzymes that have properties rivaling those of natural systems. The talk will also explore departmental and educational changes that have led to the recent successes in protein design as a model for further advances at the interface of chem. and biol.