Chemical Biology

Current Research Areas

The Biological Chemistry research group collaborate as members of the Centre for Chemical Biology, comprising of staff from the Departments of Biochemistry and Chemistry. The Centre uses a wide range of chemical approaches and ideas, including molecular structure and modelling, spectroscopy, kinetics and synthesis in a variety of research areas.
Further details of the current research areas of Molecular Enzymology, Structural Biology and Synthetic Chemistry can be found below.

Molecular Enzymology

We use kinetic, spectroscopic, potentiometric, single molecule imaging and protein engineering methods to study the mechanisms of a number of redox enzymes and motor proteins. Target enzymes include novel proteins identified from genome sequencing projects in addition to more established enzyme systems. The techniques are used in close collaboration with structural biology and computer modelling studies within the Centre for Chemical Biology.

Biological questions addressed

Hydrogen tunnelling in enzymes - spearheading a major paradigm shift
Mechanisms of biological electron transfer
Mechanism of muscle contraction
Behaviour of enzymes at the single molecule level
Mechanisms of the cytochrome P450 enzymes
Mechanism and function in haem (non-P450)-dependent enzymes
Mechanisms of flavin-dependent enzymes
Mechanisms of quinone-dependent enzymes

Structural Biology

We use the techniques of X-ray crystallography and NMR spectroscopy to study the structure, dynamics and interactions of biological macromolecules, principally proteins. This work is carried out in close conjunction with functional studies of the proteins, so as to explore structure-function relationships, and also often with computer modelling studies.

Enzyme structure and function studies

Substrate binding and electron transfer in redox proteins, including:

Cytochrome P450 mono-oxygenase system Morphinone reductase PETN reductase Fumarate reductase ETF
O₆Methylguanine-DNA methyltransferase - a DNA repair protein
Inhibitor binding to metallo-b-Lactamases
b-helical acyl-transferases
Dihydrofolate reductase

Synthetic Chemistry

We use synthetic chemistry to study biological processes at the molecular level. The techniques are used in close collaboration with structural biology, molecular enzymology and computer modelling studies within the Centre for Chemical Biology.

Biological questions addressed:

Molecular recognition
Protein-protein interactions
Cell transport mechanisms
Enzyme mechanisms and inhibition
Biotransformations

Techniques Used

Surface analytical techniques
Protein ligand docking
Protein engineering and recombinant DNA
Quantitative structure activity relationships
Potentiometry
Laser flash photolysis
Enzyme kinetics
Stopped-flow kinetics
Steady state kinetics
IR, UV and fluorescence spectroscopy
HPLC and GC chromatography
Mass spectrometry
NMR spectroscopy

Simulating electron transfer pathways
Molecular dynamics simulations
Comparative modelling
Hybrid quantum mechanical/molecular mechanical calculations
Single molecule methods
Equilibrium perturbation
Quenched flow
Organic synthetic methodology
Combinatorial chemistry and high-throughput methodology
Protein cloning, expresion, purification and screening
Molecular modelling mutagenesis
Reaction simulation and modelling
Amino acid sequence analysis