Computational enzymology

COMPUTATIONAL ENZYMOLOGY INSIGHTS INTO ENZYME MECHANISM AND CATALYSIS FROM MODELLING... 

Bruice TC, K Kahn (2000) Computational enzymology. Curr. Opin. Chem. Biol. 4 (5) 540-544... 

To provide a flavor of how computational chemistry has been applied to biochemical problems, this chapter focuses on a small subset of computational biochemistry, namely, computational enzymology. Presented here are some examples of how quantum chemical computations have been used to understand the mechanism of catalysis provided by enzymes. The chapter ends with a look at one of the true holy grails of biochemistry the abihty to design an enzyme for a specific purpose, to catalyze a particular reaction where nature provides no such option. 

Sinee optimization of the structure of the protein from seratch is so difficult, most computational enzymology studies begin with a known protein structure, typically from an X-ray crystallography experiment. In an ideal situation, one might hope to obtain the structure of the protein bound with its substrate, even more ideally, obtain the structure of the TS within the enzyme active site. However, since enzymes are efficient catalysts, it is impossible to isolate either of these states. Rather, the next best thing is to obtain the X-ray structure of the enzyme bound with an inhibitor. This structure can then be used as the starting point for a computational examination. 

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. 

Computational enzymology Protein tyrosine phosphatase reactions... 

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