Accessibility statement

Professor Roderick E Hubbard

+44 (0)1904 328267

Fragment and structure-based discovery


My research interests for the past 40 years have been the structure of proteins – what they look like (structure determination and molecular modelling), how they perform their function (protein-ligand interactions, mechanism of action) and how to exploit that information (design of modified proteins and drug discovery).

Over the past twenty years, the focus has been on using information about protein structures to design small molecule compounds that change the way proteins work.  I have divided my time between academic research within York Structural Biology Laboratory (activating industrial enzymes, chemical biology, structure-based design methods, fragment design) and applied research in drug discovery at the pharmaceutical company, Vernalis.  In addition, I advise several pharmaceutical and technology companies around the world.

As Emeritus Professor at York, I continue some teaching and advise on the development of chemical and structural biology research.

At Vernalis, we use the methods of structure-based drug discovery in collaboration with companies around the world to discover new compounds which can be taken forward in clinical trials to treat various diseases and conditions, including cancer, inflammation, infection and neurodegeneration (see Vernalis Research Website for details).

Key recent publications

  • Fragment-Based Discovery of Novel non-Hydroxamate LpxC Inhibitors with Antibacterial Activity.
    Yamada et al., J Med Chem.,
  • Rapid optimisation of fragments and hits to lead compounds from screening of crude reaction mixtures.
    Baker et al., Commun Chem., 2020, 3, 122
  • Water Networks Can Determine the Affinity of Ligand Binding to Proteins.
    Darby et al., J Am Chem Soc., 2019, 141, 15818-15826.
  • Increase of enzyme activity through specific covalent modification with fragments.
    Darby et al., Chem Sci, 2017, 8, 7772-7779
  • Twenty years on: the impact of fragments  on drug discovery.
    Erlanson et al., Nature Reviews Drug Discovery, 2016, 15, 605-619
  • Fragment-Based Lead Discovery.
    Hubbard R E., in RSC Medicinal Chemistry Handbook, ed A. Davis and S Morley, 20
  • rDock: A fast, versatile and open source program for docking ligands to proteins and nucleic acids.
    Ruiz-Carmona et al., PLoS Comp Biol, 2014, 10, Article Number: e1003571

Brief career summary

Apart from brief sabbaticals at Harvard, Rod Hubbard’s academic career has been at the University of York. During the 1980s he was a pioneer in the development of molecular graphics and modelling systems for studying protein structure (HYDRA and QUANTA), which introduced methods that are still in use today. In the 1990s, he helped to build (and directed) the Structural Biology Laboratory at York as a major centre, with over 80 scientists studying the structure and function of proteins.

His personal research interests have focused on understanding the relationship between structure, mechanism, and function in various protein systems (including proteases, nuclear receptors and kinases) and experimental and theoretical studies of protein-ligand interactions. Since 2001, he has spent some of his time at the company Vernalis, where he helped establish and apply fragment and structure-based drug discovery methods. He is also a consultant to several pharmaceutical and technology companies and sits on various academic advisory panels.

Five most cited papers

  1. Brzozowski, A.M., Pike, A.C.W., Dauter, Z., Hubbard, R.E., Bonn, T., Engstrom, O., Ohman, L., Greene, G.L., Gustafsson, J.A. and Carlquist, M. (1997), 'Molecular basis of agonism and antagonism in the oestrogen receptor', Nature, 389, 753-758
  2. Baker, E. N. & Hubbard, R. E. (1984) 'Hydrogen Bonding  in Globular Proteins', Progress in Biophysics and Molecular Biology, 44 97-179
  3. Hyde, S.C., Emsley, P., Hartshorn, M.J., Mimmack, M.M., Gileadi, U., Pearce, S.R., Galagher, M.P., Gill, D.R., Hubbard, R.E. and Higgins, C.F. (1990) 'Structural Model of ATP-binding proteins associated with cystic fibrosis, multidrug resistance and bacterial transport', Nature, 346 362-365
  4. Pike, A.C.W., Brzozowski, A.M., Hubbard, R.E., Bonn, T., Thorsell, A.G., Engstrom, O., Ljunggren, J., Gustafsson, J.K. and Carlquist, M. (1999) 'Structure of the ligand-binding domain of oestrogen receptor beta in the presence of a partial agonist and a full antagonist' Embo J, 18 4608-4
  5. Baker, E.N., Blundell, T.L., Cutfield, J.F., Cutfield, S.M., Dodson, E.J., Dodson, G.G., Hodgkin, D.C., Hubbard, R.E., Isaacs, N.W., Reynolds, C.D., Sakabe, K., Sakabe, N., Vijayan, M. (1988) 'The structure of 2Zn insulin at 1.5A resolution' Phil. Tran. R. Soc. Lond, B319, 369-456