Based on the electrostatic patterns computed for the M-cluster, we expect the protein matrix to induce a preference for H2S/HS -coordination to Fe2 over Fe6. Consequently, the free coordination site at Fe6 would be available for N2-binding. Gratifyingly, these qualitative predictions are borne out by QM/MM computations by Bjornsson et al. for 3U7Q. In Head-Gordon's work based on a relatively large cluster model, a preference for cleavage of Fe6-S bond during the initial reduction is computed as well (note that in subsequent catalytic steps, they inadvertently display H2S-Fe6 instead). This qualitative electrostatic analysis thus recovers the trends predicted with more advanced simulations. Importantly, it reveals the role of OLEFs during the nitrogen-reduction cycle at the FeMoco. Although N2 coordination to Fe6 is seemingly not electrostatically promoted (as the faint electric field points in the wrong direction to induce stabilization here), the overall nitrogen fixation process is. Indeed, the OLEF favors the rupture of the Fe2-µS-Fe6 bridge, through a pronounced negative field at Fe6, i.e., the site to which the terminal SH - /H2S most likely coordinates, prior to being released. Note that recent experiments by Einsle and co-workers confirm the pronounced lability of the Fe2-µ2-S2B-Fe6 bridge, compared to the other µ 2 -or µ 3 -sulfide bridges present in the M-cluster. Based on the full reaction profiles recently reported by Head-Gordon et al., 2 one can better understand why the formation of the terminal -SH/H2S species, with an exposed Fe primed for N2 coordination, is likely a critical step that needs to be markedly stabilized by the protein environment surrounding the M-cluster: in their calculations, the E4 state, i.e., the quadruply reduced state of the FeMoco is generated right before N2 coordination takes place.