Undergraduate Course

Department of Chemistry University of Oxford

Research Topics and Supervisors willing to supervise Chemistry Part II students.

Prof. Philip Biggin (Biochemistry Department) philip.biggin@bioch.ox.ac.uk

Computational Drug Design.
We are interested in developing and applying computational methods to drug design.  Methods range from rigorous alchemical thermodynamic calculations through to machine learning.  Where possible the calculations are linked to ongoing work in Oxford or industrial partners.

References:-

1. Large-scale analysis of water stability in bromodomain binding pockets with grand canonical Monte Carlo.
Aldeghi M, Ross GA, Bodkin MJ, Essex JW, Knapp S, Biggin PC.
Commun Chem. 2018 Apr 5;1. pii: 19. doi: 10.1038/s42004-018-0019-x.

2. Statistical Analysis on the Performance of Molecular Mechanics Poisson-Boltzmann Surface Area versus Absolute Binding Free Energy Calculations: Bromodomains as a Case Study.
Aldeghi M, Bodkin MJ, Knapp S, Biggin PC.
J Chem Inf Model. 2017 Sep 25;57(9):2203-2221. doi: 10.1021/acs.jcim.7b00347. Epub 2017 Aug 24.

3. Predictions of Ligand Selectivity from Absolute Binding Free Energy Calculations.
Aldeghi M, Heifetz A, Bodkin MJ, Knapp S, Biggin PC.
J Am Chem Soc. 2017 Jan 18;139(2):946-957. doi: 10.1021/jacs.6b11467. Epub 2017 Jan 9.

4. Accurate calculation of the absolute free energy of binding for drug molecules.
Aldeghi M, Heifetz A, Bodkin MJ, Knapp S, Biggin PC.
Chem Sci. 2016 Jan 14;7(1):207-218. Epub 2015 Oct 7.

 

Prof. Mark Howarth (Biochemistry Department) mark.howarth@bioch.ox.ac.uk , http://www.bioch.ox.ac.uk/howarth
Bionanotechnology for intelligent cell activation and vaccination.
Particular projects include solid-phase synthesis of polypeptide teams, for controlled triggering of cancer cell death or magnetic cancer cell capture for early diagnosis; also adapting auto-catalysed amide bond formation from bacteria to make “protein superglues” to engineer viral particles for new kinds of vaccine. Techniques that may be used: chemical modification of proteins, cell culture, fluorescence microscopy, mass spectrometry, DNA manipulation (PCR, cloning, mutagenesis), protein design and evolution, X-ray crystallography. 
References:
Nanoteamwork: covalent protein assembly beyond duets towards protein ensembles and orchestras. Banerjee A, Howarth M. Curr Opin Biotechnol. 2018 Jun;51:16-23
Plug-and-Display: decoration of Virus-Like Particles via isopeptide bonds for modular immunization. Brune KD, Leneghan D, Brian IJ, Ishizuka AS, Bachmann MF, Draper SJ, Biswas S, Howarth M. Sci Rep 2016 Jan 19;6:19234.

 

Prof. Christina Redfield (Biochemistry Department) christina.redfield@bioch.ox.ac.uk

http://www.bioch.ox.ac.uk/aspsite/index.asp?pageid=596
High-field NMR (500-950 MHz) is used to study the structure, dynamics, interactions and folding of proteins in solution.
L.J. Smith, A. Bowen, A. DiPaolo, A. Matagne and C. Redfield, The Dynamics of Lysozyme from Bacteriophage Lambda in Solution probed by NMR and MD simulations, ChemBioChem 14, 1780-1788 (2013).
D.A. Yadin, I.B. Robertson, J. McNaught-Davis, P. Evans, D. Stoddart, P.A. Handford, S.A. Jensen and C. Redfield, Structure of the fibrillin-1 N-terminal domains suggests heparan sulphate regulates the early stages of microfibril assembly, Structure 21, 1743-1756 (2013). D.A.I. Mavridou, E. Saridakis, P. Kritsiligkou, E.C. Mozley, S.J. Ferguson and C. Redfield, An extended active-site motif controls the reactivity of the thioredoxin fold. J. Biol. Chem. 289, 8681-8696 (2014).
P.C. Weisshuhn, D. Sheppard, P. Taylor, P. Whiteman, S.M. Lea, P.A. Handford and C. Redfield, Non-linear and flexible regions of the human Notch-1 extracellular domain revealed by high-resolution structural studies, Structure, 24, 555-566 (2016).

 

Prof. Ioannis Vakonakis (Structural Biology and Biophysics, Biochemistry Department)
ioannis.vakonakis@bioch.ox.ac.ukhttp://www.bioch.ox.ac.uk/vakonakislab/
My group seeks to develop novel inhibitors against key enzymes of the malaria parasite. We are interested in targeting enzymes involved in a broad range of parasite functions, including chaperone proteins that enhance malaria virulence and enzymes involved in haemoglobin digestion by the parasite. We are structural biologists and biochemists, primarily using X-ray crystallography and solution-state NMR to understand these enzymes at the atomic level, and then developing in vitro biochemical assays of function. We collaborate with Oxford-based high-throughput pipelines (XChem and OxXChem) and an industrial partner (CloudPharm) for the in vitro and in silico identification and development of small molecules binding to our enzymatic targets, once the enzyme structure is elucidated.

  • Cutts, E.E., Laasch, N., Reiter, D.M., Trenker, R., Slater, L.M., Stansfeld, P.J., Vakonakis, I. (2017) Structural analysis of P. falciparum KAHRP and PfEMP1 complexes with host erythrocyte spectrin suggests a model for cytoadherent knob protrusions. PLoS Pathog. 13, e1006552.
  • Oberli, A., Zurbrügg, L., Rusch, S., Brand, F., Butler, M.E., Day, J.L., Cutts, E.E., Lavstsen, T., Vakonakis, I., Beck, H.P. (2016) Plasmodium falciparum PHIST Proteins Contribute to Cytoadherence and Anchor PfEMP1 to the Host Cell Cytoskeleton. Cell Microbiol. 18, 1415-28.
  • Oberli, A., Slater, L.M., Cutts, E., Brand, F., Mundwiler-Pachlatko, E., Rusch, S., Masik, M.F.G., Erat, M.C., Beck, H.P., Vakonakis, I. (2014) A Plasmodium falciparum PHIST protein binds the virulence factor PfEMP1 and co-migrates to knobs on the host cell surface. FASEB J. 28, 4420-33.