De Novo Design of Enzymes

Bohm HJ. The computer program LUDI a new method for the de novo design of enzyme inhibitors. J Comput Aided Mol Design 1992 6 61-78. 

De novo design of enzyme inhibitors by Monte Carlo ligand generation, J. Med. Chem. 38 466 (1995). 

A major addition to the second edition is Chapter 9, which discusses computational enzymology. This chapter extends the coverage of quantum chemistry to a sister of organic chemistry—biochemistry. Since computational biochemistry truly deserves its own entire book, this chapter presents a flavor of how computational quantum chemical techniques can be applied to biochemical systems. This chapter presents a few examples of how QM/MM has been applied to understand the nature of enzyme catalysis. This chapter concludes with a discussion of de novo design of enzymes, which is a research area that is just becoming feasible, and one that will surely continue to develop and excite a broad range of chemists for years to come. 

H.-J.Bohm.y. Comput.-Aided Mol. Design, 6, 61 (1992). The Computer Program LUDI A New Method for the De Novo Design of Enzyme Inhibitors. 

The base-catalyzed decomposition of benzisoxazoles to yield 2-cyanophenols (also called the Kemp ehmination. Figure 12) is a reaction that still fascinates researchers, even though it was first reported more than a century ago. The Kemp elimination (an E2 reaction) is not catalyzed by any known natural enzyme but it has been widely used for some time as a prototypical reaction for proton transfer from carbon, and very recently, has been one of the choices, and probably the most successful one (although far from perfect), for the de novo design of enzymes through the aid of computers.Its popularity is certainly facilitated by the ease of preparation of benzisoxazoles from salicylaldehydes, " and by the fact that the... 

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