pH-dependent permeability of outer membrane protein G: an in silico study

Outer membrane protein G (OmpG) is a monomeric protein of E. coli outer membrane that mediates a pH-dependent non-specific oligosaccharide transport [1]. Two X-ray structures have been determined at different pH values: a closed conformation at low pH that inhibits metabolite transport; and an open one at neutral pH that allows it [1,2]. The key structural difference behind the mechanism lies in the position of the external loops, that determine the open or closed conformation of the channel. Given the important function of this protein, a detailed description of the conformation changes that result from varying the pH has enormous biological relevance, possibly contributing in making it a better antibiotic target and more flexible biosensor [3]. Here, we will perform constant pH molecular dynamics (CpHMD) simulations of a membrane-embedded OmpG in order to characterize the conformational/protonation space of both end states (open and closed). pH-induced conformational transitions and metabolite transmembrane diffusion through the pore are examples of other objectives in the current project.

[1] Yildiz, Ö., Vinothkumar, K.R., Goswami, P., Kühlbrandt, W. EMBO J., 2006, 25, 3702

[2] Zhuang, T., Chisholm, C., Chen, M., Tamm, L.K. J.Am.Chem.Soc., 2013, 135, 15101

[3] Chen, M., Khalid, S., Sansom, M. S., Bayley, H. Proc. Natl. Acad. Sci. U.S.A., 2008, 105, 6272.