Complementary computational and experimental work is proposed to elucidate the biocatalytic properties of C. fumago chloroperoxidase (CCPO) and develop improved mutants for chiral synthesis. In particular, the work aims to determine the properties of CCPO's active site that lead to highly enantiospecific epoxidation using docking and MD computational techniques, and on that basis, to predict, synthesize, and assay mutants with improved enantiospecificity. Secondly, a QM and QM/MM study of the halogenation mechanism of CCPO is proposed in order to elucidate the mechanism, which has long been disputed. Halogenation is important for pharmaceutical synthesis and may also have significance for CCPO's epoxidation reaction. Both aspects of the proposed research will help construct synthetic routes to drugs with possible significant impact on human health.
