Focusing the Computational Microscope on the Cell Envelopes of Gram-negative Bacteria

A protective cell envelope surrounds Gram-negative bacteria such as E. coli, providing a selective gateway connecting the interior of the cell to the external environment. We employ molecular dynamics simulations, at multiple levels of resolution,  to reveal the details of covalent and non-covalent interactions of proteins, lipids, and sugars within the cell envelope to gain insights into how these molecules function individually ,and also together as a whole. We use data such X-ray, NMR and cryoEM structures from our structural biology colleagues, and combine them with molecular models that represent the in vivo environment of the bacterium to study their dynamics. We have used coarse-grain models based on cryoEM data to reveal the differences in correlation between protein and lipid motion as a function of membrane and protein type. More recently we have built an atomistic model of the E. coli cell wall, and have explored the interactions of inner and outer membrane proteins with the peptidoglycan that comprises the wall.  We are interested in talking to colleagues about hybrid models for future work.

References:

1-  Hsu PC, Samsudin F, Shearer J, Khalid S, (2017) “It Is Complicated: Curvature, Diffusion, and Lipid Sorting within the Two Membranes of Escherichia coli.” J Phys Chem Lett. 8 (22), 5513-5518

2-  Samsudin F, Boags A, Piggot TJ, Khalid S. (2017), “Braun’s Lipoprotein Facilitates OmpA Interaction with the Escherichia coli Cell Wall”. Biophys J 113 (7) 1496-1504

3-  Hsu PC, Bruininks BMH, Jefferies D, Cesar Telles de Souza P, Lee J, Patel DS, Marrink SJ, Qi Y, Khalid S, Im W. (2017), “CHARMM-GUI Martini Maker for modeling and simulation of complex bacterial membranes with lipopolysaccharides”. J. Comput. Chem. 38 (27) 2354-2363

4-  Boags A, Hsu PC, Samsudin F, Bond PJ, Khalid S (2017). “Progress in Molecular Dynamics Simulations of Gram-Negative Bacterial Cell Envelopes.” J. Phys Chem Lett. 8 (11) 2513-2518

More on the Syma Khalid Research Group.