Enzyme specificity, evolution

It also seems clear that specific interactions (which are used by natural enzymes) are missing from even the more sophisticated systems. This could be a problem if we want to mimic natural enzymes, or if we want to use (complex) model systems to understand the power of natural enzymes. But overall, there is no need for artificial design to replicate what we know about enzymes—artificial evolution might as well proceed toward a route unexplored by Nature. Although specific interactions are important for natural enzymes, or enzymes involved in metabolic pathways for which there needs to be discrimination, there are other processes for which such discrimination might not be crucial. Degradation of pollutants is an obvious... 

This study is particularly noteworthy in the evolution of QM-MM studies of enzyme reactions in that a number of technical features have enhanced the accuracy of the technique. First, the authors explicitly optimized the semiempirical parameters for this specific reaction based on extensive studies of model reactions. This approach had also been used with considerable success in QM-MM simultation of the proton transfer between methanol and imidazole in solution. 

Serine proteinases such as chymotrypsin and subtilisin catalyze the cleavage of peptide bonds. Four features essential for catalysis are present in the three-dimensional structures of all serine proteinases a catalytic triad, an oxyanion binding site, a substrate specificity pocket, and a nonspecific binding site for polypeptide substrates. These four features, in a very similar arrangement, are present in both chymotrypsin and subtilisin even though they are achieved in the two enzymes in completely different ways by quite different three-dimensional structures. Chymotrypsin is built up from two p-barrel domains, whereas the subtilisin structure is of the a/p type. These two enzymes provide an example of convergent evolution where completely different loop regions, attached to different framework structures, form similar active sites. 

Several other enzymes have been investigated by directed evolution in order to control substrate specificity, although most of the studies are at an early stage. These... 

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