Influence of subunit structure on the oligomerization state of light-harvesting complexes: A free energy calculation study

Light harvesting complexes 2 (LH2) from Rhodospirillum (Rs.) molischianum and Rhodopseudomonas (Rps.) acidophila form ring complexes out of eight or nine identical subunits, respectively. Here, we investigate computationally what factors govern the different ring sizes. Starting from the crystal structure geometries, we embed two subunits of each species into their native lipid-bilayer/water environment and investigate their dynamics by means of both equilibrium and non-equilibrium (steered) molecular dynamics simulations. For each species, by employing the umbrella sampling method, we calculate and compare the free energy profiles, as a function of the angle between the two subunits, for two representative separations of the subunits. We find that two subunits prefer to arrange at distinctly different angles, depending on the species, at about 45° for Rs. molischianum and at about 38.5° for Rps. acidophila, which is likely to be an important factor contributing to the assembly into different ring sizes. Our calculations suggest a key role of surface contacts within the transmembrane domain in constraining these angles, whereas the strongest interactions stabilizing the subunit dimers are found in the C-, and to a lesser extent, N-terminal domains. The presented computational approach provides a promising starting point to investigate the factors contributing to the assembly of protein complexes, in particular if combined with modeling of genetic variants.