We are based in the Unilever Centre for Molecular Informatics. Our research is focused on the development and application of computational methods to the study of biomolecular systems. In particular, molecular simulations are being used to understand the "biological machinery" essential to fundamental cellular processes such as folding, transport, and signalling, as well as to identify the causes of associated diseases.
Key areas of research include:
The interplay between local environment and macromolecular structure/function relationships.
Proteins are found in different subcellular compartments, may be associated with other biomolecules, and are sometimes captured in non-native phases such as detergent micelles, lipid vesicles, or crystalline arrays to enable in vitro studies. Simulations of such macromolecular assemblies help to relate their conformation and dynamics to function.
Large-scale conformational changes in multi-domain proteins.
Such changes enable the formation of complex signalling networks; individual proteins or domains are sensitive to particular stimuli, such as non-covalent ligand recognition or post- translational modification, and subsequently undergo structural changes that lead to a downstream response. Simulations of such events benefit from approaches that bias sampling along defined conformational pathways within the free energy landscape.
The self-assembly mechanisms of biomolecules.
Particular emphasis is being placed on protein-protein and protein-lipid interactions, which are involved in e.g. cellular signalling, membrane transport, or antimicrobial activity. Studying such processes benefits from a multi-scale approach, whereby coarse-grained (CG) models help to simplify complex systems and enable simulation of long timescale assembly processes.
These involve a simplified description of a particular molecular system that nevertheless allows useful predictions to be made. Examples include studying the effect of in silico mutations upon the folding or membrane partitioning equilibria of protein fragments, or the use of core models of naturally-occurring membrane channels as biomolecule sensors in nanotechnology (an ongoing collaboration with Dr S. Khalid's group at the University of Southampton).
A full publication list can be found here.