Research Interests

  • Molecular structure, flexibility and recognition

    At the heart of most of our research activities is the development and application of state-of-the-art molecular simulation methods to the study of the structure, dynamics, and recognition properties of complex molecular systems. Most commonly these are biomolecular systems (proteins and/or nucleic acids), but we also apply the methods in other areas (e.g. drug-polymer complexes). Some of our research is quite 'blue-skies', related to understanding the fundamental principles behind the relationship between molecular structure and dynamical behaviour, while other projects are collaborative activities with experimental groups aimed at discovering and developing new drugs.

    We are part of CCPBioSim - The Collaborative Computational Project for Biomolecular Simulation, and of ABC - The Ascona B-DNA Consortium.

  • New simulation and analysis methods

    There is a constant drive for faster and more efficient molecular simulation methods, but also as a result a pressing need for effective methods to extract the maximum amount of useful information from the enormous amounts of raw data such simulations produce. As part of the EPSRC/NSF funded UK/US ExTASY project postdoc Ardita Shkurti is developing new software tools for the production and effective data mining of large molecular dynamics trajectory data sets. This project is leveraging and extending some of the publicly available software we have previously developed, for example the PCA-based compression and analysis toolkit PCAZIP and the ensemble analysis and enrichment tool COCO.

  • Drug-polymer interactions and self-assembly

    Techniques that were first applied in the area of biomolecular simulation are now being used to study other types of large complex systems, particularly drug-polymer complexes. As part of a multidisciplinary EPSRC-funded project (with Marin Garnett, Cameron Alexander, and Jonathan Burley, and industrial partner AstraZeneca), postdoc Eleanor Turpin is developing multiscale simulation methods for the study of the structures and properties of drug-polymer solid dispersions for novel formulations. PhD student Robbie Mackenzieis examining how coarse-grained simulation methods designed originally to study the self-assembly of protein/lipid bilayer systems may be used to predict the assembly, structure and properties of drug-polymer nano particles (also with AZ). PhD student Ioanna Styliari is looking at how certain polymer drug delivery systems agglomerate using both simulation and experimental methods (with GSK).

  • The telomere as a target for novel antitumour agents

    Our expertise in the prediction and analysis of both DNA and protein structure, dynamics, and recognition is brought together in our work investigating the telomere as a novel target for antitumour agents. This programme of work involves many collaborators both within the University and outside. Projects include inhibitors of telomeric protein-protein interactions (PhD student Twana Salih with Weng Chan and Lodewijk Dekker) and G-quadruplex ligands that destabilize telomeres (PhD student Maysaa Saleh with Chris Moody).

  • Discovery and evaluation of small-molecule mitotic kinases inhibitors

    Although most of our projects have a computational focus, this is not always the case. For example, PhD student Tianging Lu's project (in collaboration with Tracey Bradshaw) is aimed at the design, synthesis and evaluation of novel small-molecule inhibitors based on ON01910.Na, which is under III clinical trial and selectively targets PI3K and PLK pathways. By modifying the structure of ON01910.Na, a novel class of (E)-styrylsulfonyl methylpyridine derivatives with improved oral bioavailability has been designed and synthesised (patent WO2011/161446, 2011). Tiangong is now working to unravel the complex mechanism of action of these molecules.