Dynamics of OmpF Trimer Formation in the Bacterial Outer Membrane of Escherichia coli.

The self-assembly of outer membrane protein F (OmpF) in the outer membrane of Escherichia coli Gram-negative bacteria was studied using multiscale molecular dynamics simulations. To accommodate the long time scale required for protein assembly, coarse-grained parametrization of E. coli outer membrane lipids was first developed. The OmpF monomers formed stable dimers at specific protein-protein interactions sites irrespective of the lipid membrane environment. The dimer intermediate was asymmetric but provided a template to form a symmetric trimer. Superposition analysis of the self-assembled trimer with the X-ray crystal structure of the trimer available in the protein data bank showed excellent agreement with global root-mean-square deviation of less than 2.2 Å. The free energy change associated with dimer formation was -26 ± 1 kcal mol-1, and for a dimer to bind to a monomer and to form a trimer yielded -56 ± 4 kcal mol-1. Based on thermodynamic data, an alternate path to trimer formation via interaction of two dimers is also presented.