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 angstrom. The free energy change associated with dimer formation was -026 +/- 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.