On Dioxygen and Substrate Access to Soluble Methane Monooxygenases: An all-Atom Molecular Dynamics Investigation in...

In a preliminary exploration of the dummy model for diiron proteins, random-acceleration molecular dynamics (RAMD) revealed that a pure four-helix bundle structure, like hemerythrin, constitutes an efficient cage for dioxygen (O₂ ), which can only leave from defined, albeit very broad, gates. However, this well ordered structure does not constitute an archetype on which to compare O₂ permeation of other diiron proteins, like the complex of soluble methane monooxygenase hydroxylase with the regulatory protein (sMMOH-MMOB). The reason is that with this complex, unlike hemerythrin, the four helices of the four-helix bundle are heavily bent, and RAMD showed that most traps for O₂ lie outside them. It was also observed that, in spite of a nearly identical van der Waals radius for O₂ and the natural substrate CH₄ , the latter behaves under RAMD as a bulkier molecule than O₂ , requiring a higher external force to be brought out of sMMOH-MMOB along trajectories of viable length. All that determined with sMMOH-MMOB multiple gates and multiple pathways to each of them through several binding pockets, for both O₂ and CH₄ . Of the two equally preferred pathways for O₂ , at right angle with one another, one proved to be in accordance with the Xe-atom mapping for sMMOH. In contrast, none of the pathways identified for CH₄ proved to be in accordance with such mapping, CH₄ looking for more open avenues instead.