A Summer of Simulations

Figure 1: Snapshots from a coarse-grained MD (left) and from a mesoscale (right) simulation of bacterial outer membrane protein clustering (Click image to enlarge)

Three recent papers from the Sansom group reveal how molecular simulations can complement experimental studies in advancing our understanding of membrane protein interactions underlying membrane organization and function.

Collaborative research with Carol Robinson’s group (Chemistry) employs molecular simulations to aid the design and interpretation of mass spectrometry-based experiments. The study, published in Nature, uncovers a new role for phosphatidylinositol 4,5-bisphosphate (PIP2) lipids in the modulation of signalling by G-Protein Coupled Receptors

As part of an ongoing collaboration with Yvonne Jones’ group in STRUBI, Chavent et al use simulations to reveal interactions of the EphA2 receptor tyrosine kinase with the intracellular surface of a model cell membrane. The study, published in Structure, shows how phosphatidylinositol phosphates (PIPs) mediate interaction of the EphA2 kinase domain with the membrane, whilst kinase and juxta-membrane domains induce formation of nanoclusters of PIP molecules. These results enable computational reconstitution of a near complete EphA2 receptor model.  

A collaboration between the Sansom and Kleanthous groups in Biochemistry along with colleagues in Mathematics uses simulations to explore the molecular basis of clusters (or ‘islands’) of proteins found in E. coli outer membranes. The study, published in Nature Communications, uses a combination of coarse grained molecular dynamics and a novel mesoscale simulation methodology to model the dynamic formation of micrometer scale clusters, providing a molecular explanation of the experimentally observed restricted diffusion of outer membrane proteins.

Overall, these studies emphasize the power and potential of simulations to advance our understanding of membrane organization, linking membrane protein structure and cellular function.