Selected Publications

Matthew J. Cliff, Richard Harris, David Barford, John E. Ladbury and Mark A. Williams (2006). Conformational diversity in the TPR domain mediated interaction of protein phosphatase 5 with Hsp90. Structure 14, 415-426.

Matthew J. Cliff, Mark A. Williams, David Barford, John E. Ladbury (2005). Molecular recognition via coupled folding and binding in a TPR domain. J. Mol. Biol. 346, 717-32.

Mark A. Williams & John E. Ladbury (2004). The extended interface: measuring non-local effects in biomolecular interactions. Curr Opin Struct Biol. 14, 562-9.

Research Interests

Research in my group aims to understand protein structure-function relationships in basic cellular processes and disease states. Through a multi-disciplinary approach using biophysical and structural experimental methods, structural bioinformatic analysis and physics-based molecular simulation, we aim to develop as complete as possible an understanding of the formation of biomolecular complexes. We aim to ulitise this knowledge to combat disease via structure-based drug discovery and design, particularly in the area of anti-microbial therapy.

  • Physical Processes in Biomolecular Complex Formation
  • Investigation of the changes in structure, dynamics and thermodynamics that accompany complex formation. Techniques applied include NMR and IR spectroscopies and microcalorimetry

  • Protein Structure in Solution
  • Determination of the structures of proteins and protein-ligand complexes using nuclear magnetic resonance spectroscopy. Present emphasis is on essential microbial proteins that may be useful targets for antimicrobial therapy. Other projects include proteins involved in eukaryotic cell signalling and cancer.

  • Structural Bioinformatics
  • Database and structural analysis projects using the data from the PDB and the scientific literature to investigate structure-thermodynamic relationships.

  • Molecular Simulation
  • Use and development of a wide variety of computational techniques to aid in the interpretation and prediction of experimental data on the interplay between structure, kinetics and thermodynamics on scales ranging from the molecular to cellular.

  • Drug Discovery & Design
  • Identification of lead compounds through combined use of comutational and experimental fragment based screening methods. Methods for predicting binding free energies.

  • Group Members & Collaborators