Our major research programme concerns the folding, stability and activity of proteins. We apply a broad multi-disciplinary approach that combines methods and ideas of molecular biology and physical-organic chemistry. We use techniques including protein engineering, DNA cloning, sequencing and mutagenesis, cell culture, gene and peptide synthesis, spectroscopy, rapid reaction techniques, multi-dimensional NMR (we have a 500, 600, 700 and an 800 MHz spectrometers) and x-ray protein crystallography.

Current major projects include: protein folding, misfolding and disease; drug discovery; and structure-activity relationships of proteins involved in cancer and disease.

Although now emeritus, I am still fully active in research with long term funding, including an MRC Programme Grant.

Publications

Side-Chain Determinants of .beta.-Sheet Stability
DE Otzen, AR Fersht
Biochemistry
(2002)
34
A Calorimetric Study of the Thermal Stability of Barstar and Its Interaction with Barnase
JC Martínez, VV Filimonov, PL Mateo, G Schreiber, AR Fersht
Biochemistry
(2002)
34
Enzyme hyperspecificity. Rejection of threonine by the valyl-tRNA synthetase by misacylation and hydrolytic editing.
AR Fersht, MM Kaethner
Biochemistry
(2002)
15
Analysis of the role of the KMSKS loop in the catalytic mechanism of the tyrosyl-tRNA synthetase using multimutant cycles.
EA First, AR Fersht
Biochemistry
(2002)
34
BACKBONE DYNAMICS OF CHYMOTRYPSIN INHIBITOR .2. EFFECT OF BREAKING THE ACTIVE-SITE BOND AND ITS IMPLICATIONS FOR THE MECHANISM OF INHIBITION OF SERINE PROTEASES
GL Shaw, B Davis, J Keeler, AR Fersht
Biochemistry
(2002)
34
Active site titration and aminoacyl adenylate binding stoichiometry of aminoacyl-tRNA synthetases
AR Fersht, JS Ashford, CJ Bruton, R Jakes, GL Koch, BS Hartley
Biochemistry
(2002)
14
Mechanism of the -chymotrypsin-catalyzed hydrolysis of specific amide substrates.
AR Fersht
Journal of the American Chemical Society
(2002)
94
PROTEIN-FRAGMENTS AS MODELS FOR EVENTS IN PROTEIN-FOLDING PATHWAYS - PROTEIN ENGINEERING ANALYSIS OF THE ASSOCIATION OF 2 COMPLEMENTARY FRAGMENTS OF THE BARLEY CHYMOTRYPSIN INHIBITOR-2 (CI-2)
J Ruiz-Sanz, G de Prat Gay, DE Otzen, AR Fersht
Biochemistry
(2002)
34
Analysis of the mechanism of assembly of cleaved barnase from two peptide fragments and its relevance to the folding pathway of uncleaved barnase
AD Kippen, AR Fersht
Biochemistry
(2002)
34
Demonstration of two active sites on a monomeric aminoacyl-tRNA synthetase. Possible roles of negative cooperativity and half-of-the-sites reactivity in oligomeric enzymes.
AR Fersht
Biochemistry
(2002)
14