Discussion and Outlook

The implementations discussed in the present chapter need to be extended when electronic coupling between the two Umiting states DH-A and D-HA become important. In such a situation, explicit coupling of the PESs involved becomes necessary. Such extensions are possible even within the language of force fields. 

Robust force field implementations to follow reactive processes are an excellent means to allow accurate simulations while allowing for extensive sampling of configuration space. Although certain compromises as to their accuracy must be accepted, such procedures provide important insights into the reaction dynamics, which can be refined by using more accurate approaches such as ab initio calculations. In order to encourage more widespread use of these methods, the implementation needs to evolve from specific apphcations to allow broader applications, which will eventually make such calculations more robust and accepted. 

The authors wish to acknowledge the continued financial support from the Schweiz-erischer Nationalfonds through Grant 200021-117810 and the NCCR MUST. 

Hydrogen-Transfer Reactions, Wiley-VCH Verlag GmbH, Weinheim. 

Kaposta, C., Neumark, D.M., and Woste, L. (2003) Gas-phase infrared spectrum of the protonated water dimer. Science, 299 (5611), 1375-1377. 

From the results mentioned above, it can be proposed that a detailed investigation of different ThDP-dependent enzymes using substrate and protein engineering, with the focus on new transformations, will open new perspectives in catalytic 

Until now only TK [49a], PDC [49b], BFD, BAL [72], and mutants thereof have been investigated systematically with regard to preparative transformations. Numerous other ThDP-dependent enzymes are capable of catalyzing different asymmetric reactions as well [73]. 

As an outcome of the investigation of the biocatalytic strategies described in this chapter several new aspects with broad applicability in synthetic organic chemistry have been established  

In addition, new impacts with regard to biocatalysis have been determined  

the intrinsic property of diversity found in natural product biosynthesis has been used successfully as a model in the development of biocatalyc strate- 

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Seelbach, C. Wandrey, Industrial Biotransformations, Wiley-VCH, Weinheim 2000. 

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