Abstract
The first part of this review article lists examples of complete, empirical de novo design that made important contributions to the development of the field and initiated challenging projects. The second part of this article deals with computational design of novel enzymes in native protein scaffolds; active designs were refined through random and site-directed mutagenesis producing artificial enzymes with nearly native enzyme- like activities against a number of non-natural substrates. Combining aspects of de novo design and biological evolution of nature's enzymes has started and will accelerate the development of novel enzyme activities.
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