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Russell Group (Visiting)

Structural bioinformatics

Russell Group

Schematic outlining our approach for finding protein linear motifs that mediate protein-protein interactions. Sets of proteins (A-F) sharing an interaction partner (X) are grouped and domains and homologous sequences are removed. We then search for 3-8 residue motifs that are over-represented in the remaining sequence, and score these by a binomial probability to give a ranked set of candidate motifs mediated the interaction with protein X.

Previous and current research

Our research is focused broadly on the relationships between protein three-dimensional (3D) structure, function and evolution. A major interest over the past four years has been to develop methods to understand and predict the molecular details for macromolecular interactions. These efforts can be currently classified into three main areas.

Protein interactions and complexes: Protein interaction networks are central to any understanding of cellular processes, and though many thousands are now known, few initiatives to uncover them pay much attention to one of the best sources of data available: complexes of known 3D structure. We thus study protein interactions by considering known 3D structures. We use 3D complexes to interrogate interactions identified by other methods (e.g. yeast twohybrids) and to predict specific interactions within protein families. A major initiative in the group is related building as complete models as possible for all interacting proteins and complexes in a whole cell.

Protein and DNA sequence motifs mediating interactions: A major current challenge in biology is to discover and understand short protein or nucleic acid stretches that mediate functional interactions. We currently search for new protein-peptide and microRNA target sequences in genomes using a variety of techniques. Both methods already make fascinating predictions of biological phenomena and provide a wealth of information for people working with such sequences experimentally. We are also actively involved in experimental efforts to test or validate our predictions, either doing them ourselves or working in close collaboration with experimental groups.

Chemical biology: linking chemicals to pathways: We are now actively developing a database of chemicals linked to proteins in order to interrogate the likely effects of disrupting pathways with chemicals. This will be complemented by new and existing methods for the design of small-molecule or peptide inhibitors with the aim of working closely with experimentalists.

Future projects and goals

  • To develop the 'one-stop-shop' for structural information on currently available information (predicted or experimental) on large protein complexes. This will involve development and application of new methods for complex structure prediction.
  • To devise techniques to predict peptide binding sites on protein surfaces to complement our predictions of interacting peptides.
  • To derive methods to predict the outcome of chemical treatment on particular pathways by cross-referencing chemicals with pathway components.