Phosphate and Sulfate Chemistry
Phosphate ester hydrolysis is the building block of life, being involved in a range of processes from signal and energy transduction, to DNA and RNA synthesis and protein synthesis. As such, phosphoryl transfer reactions have been the subject of several decades of intensive experimental and computational studies. Despite this, the precise mechanism by which the hydrolysis of such compounds proceeds remains controversial. Part of the challenge lies in the fact that phosphate hydrolysis can proceed through multiple viable mechanisms, which cannot be conclusively and unambiguously distinguished between by means of experimental approaches alone. One of the central areas of interest in the Kamerlin group is the application of theoretical physical organic chemistry to computational enzymology, with a particular focus on phosphoryl and sulfuryl transfer reactions in solution and in enzymes. Specifically, our interest is in mapping catalytic promiscuity across enzyme superfamilies. In particular, we have focused on the alkaline phosphatase superfamily, the members of which are multi-promiscuous and catalyze a range of phosphoryl, sulfuryl and related group transfer reactions. This will greatly enhance our understanding of enzyme evolution, and how it can be manipulated.
Enzyme-Catalyzed Chiral Chemistry
Recent years have seen increasing appreciation of the role of enzymes as catalysts in biotechnology, and here, enzymes that can selectively catalyze reactions of industrial relevance are of great importance to the production of optically pure fine chemicals and pharmaceuticals. We work with a number of such enzymes, developing computational approaches for studying enzyme selectivity and artificial enzyme design.
In addition to enzymology, our group has a number of other (bio)chemical interests, including the structure and dynamics of epigenetically modified DNA, metal-amyloid interactions, GTP hydrolysis on the ribosome, and modeling long-range information transfer in biology.
For further information, please see our publication list.