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 (comparatively more recently) 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 (particularly the alkaline phosphatase superfamily), and harnessing the insights this provides in computational protein redesign. In this way, we are using the natural process of evolution of function to redirect enzyme activity, accelerating classical Darwinian evolution on our computers. Additional areas of interest include computational studies of enzyme catalysis and dynamics, studying the structure and dynamics of epigenetically modified DNA, as well as the development of approaches for performing ab initio QM/MM free energy perturbation. For further information, please see our publication list.