On Dioxygen Permeation of MaL Laccase from the Thermophilic Fungus Melanocarpus albomyces: An all‐Atom Molecular Dynamics Investigation

In this article, biased molecular dynamics (MD) simulations of O₂ egress from the active center of MaL laccase toward the bulk solvent were described. Parameterization of the set of four Cu(II) ions, in the framework of CHARMM‐36 FF, was carried out on a recent dummy‐atom model that takes into account the Jahn–Teller effect. By carrying out a number of statistically relevant MD simulations, under a tiny randomly oriented external force applied to the molecule O₂, three preferred gates for O₂ egress from the enzyme and a few intermediate binding pockets (BPs) for O₂ were visible; all the gates and pockets were located on two of the three domains. This wide distribution of preferred gates notwithstanding the molecule O₂ was seen to follow specific pathways, exploiting consistently the interstices created by the enzyme thermal fluctuations. These are features that can be imagined to have evolved to make MaL laccase extremely efficient as catalysts in various reactions that require O₂.