1. The Depth of Chemical Time and the Power of Enzymes as Catalysts
2. L. Pauling, Chem. Eng. News24, 1375 (1946).
3. R. L. Schowen, in Transition States of Biochemical Processes, R. D. Gandour, R. L. Schowen, Eds. (Plenum, New York, 1978), p. 77.
4. Ahistorical overview of mechanistic enzymology which serves as an excellent complement to the present analysis was published recently by Bugg ( 124 ). He points out that many enzymologists continue to search for the “elusive additional mechanisms by which enzymes may achieve high rates of catalysis” (p. 488). The thesis of the present article is that modern simulations of transition states are a powerful tool for discovering these mechanisms and that all such mechanisms can be understood in terms of various contributions to Eq. 1a. In another complementary article published after the present review was submitted Benkovic and Hammes-Schiffer ( 125 ) provide a perspective on the contributions to catalysis by focusing on the properties of DHFR.
5. H. Eyring, A. E. Stern, Chem. Rev.24, 2 (1939).