Research projects in Kamerlin Group

Our group has broad research interests that focus on applying the tools of computational biochemistry to understanding the chemical basis for complex biological problems. This spans a range of problems from understanding fundamental chemical reactivity to understanding the physicochemical parameters that allow for the evolution of new enzyme functions. Current projects in the research group include studying the role of ligand-gated conformational changes in enzyme catalysis, protein-DNA recognition, DNA proofreading and repair, enzyme evolution, GTPase regulation, the dynamical behaviour of disordered peptides, as well as the development of new approaches for computational enzymology.

Phosphate and sulphate chemistry

Phosphate ester hydrolysis is one of the most fundamental chemical reactions in living cells and is involved in a range of processes from signal and energy conversion to DNA, RNA and protein synthesis. Therefore, phosphoryl transfer reactions have been the subject of several decades of intensive experimental computational studies. Despite this, the exact mechanism of hydrolysis of phosphate esters remains controversial. Part of the challenge lies in the fact that phosphate ester hydrolysis can occur through several different mechanisms and it is impossible to distinguish between these in a conclusive and unambiguous way using experimental methods alone. One of our central research interests is the application of theoretical physical organic chemistry in computational enzymology, with a particular focus on enzyme-catalyzed phosphoryl and sulfuryl transfer reactions. By trying to map catalytic promiscuity among phosphotransferases, we hope to increase our understanding of how enzyme evolution occurs and how the process can be manipulated.

Enzyme-catalysed asymmetric synthesis

In recent years, there has been an increased interest in enzymes in the role of catalysts, especially enzymes that can selectively catalyse reactions of biotechnological and industrial significance. These enzymes are of great importance for the production of optically pure chemicals and pharmaceuticals. We work with a number of such enzymes and develop computational methods to study both their selectivity and artificial enzyme design.

Other projects

In addition to enzymology, our group has a number of other biochemical interests, including the influence of epigenetic modifications of DNA on DNA structure and dynamics, metal-amyloid interactions, GTP hydrolysis, and modeling of long-range information exchange in biological systems.