Computational Approaches to Understanding Enzymes

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. A number of research groups have employed quantum mechanics/molecular mechanics (QM/MM) methods toward understanding the activity of chorismate mutase (CM). Some examples of how quantum chemical computations have been used to understand the mechanism of catalysis provided by enzymes, are presented. The examples include the application of ab initio (both wavefunction and density functional theory (DFT)) methods toward explicating the mechanism of catalysis of enzymes. Finally, the chapter discusses developments in de novo enzyme design pioneered by the Baker and Houk laboratories.