Staff Members

Professor Andrew Hopkins FRSC Our research activities focus on developing novel informatics and experimental methods to enable new, more effective, ways of conducting drug discovery. My laboratory consists of an informatics group, that uses chemoinformatics, structural bioinforrmatics and knowledge discovery techniques in its research and an experimental biophysics group, headed by Dr Iva Navratilova, that specialises in biosensor technologies. I collaborate with the members of the University of Dundee’s Drug Discovery Unit, the ChEMBL group at the European Bioinformatics Institute (John Overington), the London School of Hygiene and Tropical Medicine (Quentin Bickle), the WHO-TDR Target Network and several pharmaceutical and biotechnology companies. Our goal is to develop novel methods and exploit them in real drug discovery programs. A summary of our current research interests is found below:

Medicinal Informatics 

Network Pharmacology

We are exploring new methods to discover and rationally design of multi-target drugs with polypharmacology.The dominant paradigm in current drug discovery is the concept of designing maximally selective ligands, to act on individual drug targets. However, many effective drugs act via modulation of multiple proteins rather than single targets. Advances in system biology are revealing a phenotypic robustness and a network structure that strongly suggests, in many cases, exquisitely selective compounds may exhibit a lower than desired efficacy in the clinic, compared to multi-target drugs. This new appreciation of the role of polypharmacology has significant implications for tackling the two major sources of attrition in drug development, namely, efficacy and toxicity.The integration of network biology and polypharmacology holds the promise of expanding the current opportunity space for druggable targets.



Chemogenomics

The growing number of available genome sequences of human pathogen allows, for the first time, the opportunity to rationally prioritize all potential drug targets for a wide range of emerging and neglected infectious diseases. However our ability to exploit a pathogen’s genome information, with the goal of identifying potential therapies for testing, is still measured in order of years, judging by the lack of progress in infectious disease therapies derived from genetic analysis. Despite the fact that our knowledge of observed attributes of the vast majority of pathogen proteins is limited or missing, our research is aimed at developing methods to prioritized potential drug targets from a pathogen genome a priori by inference from the collective wealth of bio-pharmacology knowledge available, such as genome sequences, model organism knock-outs, protein structures, medicinal chemistry structure-activity data and literature abstracts.

Translational Biology

Biosensor-based Drug Discovery

Our experimental laboratory research is focused on developing new biophysical screening methods for efficient drug discovery. We are developing biosensor based screening methods that enable us to characterise the kinetics and thermodynamics of molecular interactions. The binding kinetics of an interaction determine the affinity of a drug to its target and can impact the coupling efficiency of the drug by affecting the state of equilibrium. Therefore understanding the binding kinetics can help shape the clinical profile of a drug that are important to patients: efficacy, safety, duration of action, greater tolerability, indication and therapeutic differentiation. The sensitivity and throughput of the new generation of surface plasmon resonance (SPR) instrumentation enables this technology to be used for screening of large libraries of fragments or compounds. In particular our research is currently focused on:
• Developing the application of biosensor screening to membrane proteins, such as G-protein coupled receptors.
• Development of SPR-based fragment screening
• SPR as a method for multi-target screening
For further information on the Biosensor Laboratory’s research please see the staff page of Dr Iva Navratilova.

Image-based HTS

In collaboration with Quentin Bickle (London School of Hygiene and Tropical Medicine) and Professor Julie Frearson (Scottish Hit Discovery Facility) we are developing an imaged-based high-throughput screening system for Schistosoma mansoni. The discovery of new drugs against Schistosomiasis is hindered by the low throughput of current screening models. We are working on the developing of a high throughput screening system based on image analysis than is design to detect drugs effective against S.mansoni larvae by measurement of changes in morphology and motility of the whole organism. This project is funded by the Bill and Melinda Gates Foundation.

Selected publications:

  1. Fragment Screening by Surface Plasmon Resonance.  Iva Navratilova and Andrew L. Hopkins, ACS Med Chem Letters (2010) 1(1), DOI: 10.1021/m900002k.
  2. Predicting Promiscuity.   Andrew L. Hopkins, Nature (2009) 462(7270), 167-168.
  3. Network Pharmacology: Andrew L. Hopkins. The next paradigm in drug discovery.  Nature Chemical Biology, (2008), 4(11), 682-690
  4. Genomic-scale prioritization of drug targets: The TDR targets database.  Fernan Aguero, Bissan Al-Lazikani, Martin Aslett, Matthew Berriman, Frederick S. Buckner, Robert K. Campbell, Santiago Carmona, Ian M. Curruthers, A.W. Edith Chan, Feng Chen, Gregory J. Crowther, Maria A. Doyle, Christiane Hertz-Fowler, Andrew L. Hopkins, Gregg McAllister, Solomon Nwaka, John P. Overington, Arnab Pain, Gaia V. Paolini, Ursula Pieper, Stuart A. Ralph, Aaron Riechers, David S. Roos, Andrej Sali, Dhanasekaran Shanmugam, Wesley C. Van Voorhis and Christophe L.M.J. Verlinde,  Nature Reviews Drug Discovery, (2008), 7(11), 900-7
  5. How many drug targets are there? John P. Overington, Bissan Al-Lazikani and Andrew L. Hopkins, Nature Rev. Drug Disc. (2006) 5(12), 993-996
  6. Global Mapping of Pharmacological Space. Gaia V. Paolini, Richard H.B. Shapland, Willem P. van Hoorn, Jonathan S. Mason and Andrew L. Hopkins, Nature Biotechnology. (2006), 24(7), 805-815.
  7. Can we rationally design promiscuous drugs? Andrew L. Hopkins, Jonathan S. Mason and John P. Overington, Curr. Op. Struct. Biol. (2006) 16, 127-136.
  8. Navigating Chemical Space for Biology and Medicine. Christopher Lipinski and Andrew Hopkins, Nature (2004), 432 (7019), 855-861.
  9. Design of Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase with Improved Drug Resistance Properties. Part I. Andrew L. Hopkins, John Milton, Jingshan Ren, Richard J. Hazen, Joseph H. Chan, David K. Stammers and David I. Stuart, J. Med. Chem. (2004), 47(24), 5923-5936
  10. The Druggable Genome. Andrew L. Hopkins and Colin R. Groom, Nature Rev. Drug Disc. (2002), 1 (9), 727-730

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