A New Route for Dioxygen Activation Uncovered from Quantum Mechanics Investigations of X‐Ray‐Diffraction‐Captured Intermediates of the Ferroxidase Reaction of Ferritins from Gram‐Negative Bacteria

Abstract

Following the recent reassessment from X‐ray‐diffraction‐caught short‐path uptake to wide permeation of the S20A mutant Escherichia coli ferritin by ferrous ions, what happens when dioxygen gets to the diiron system is investigated. It is shown that the previously X‐ray‐caught situation of an unbound‐dioxygen diferrous state actually is an ephemeral state that changes into a P‐type peroxodiferric state, while a water molecule moves to bridge the two ferric ions, in what appears to be a remarkable redox process. All this stems from density functional theory (DFT)‐based quantum mechanics‐molecular mechanics and broken symmetry (BS) calculations that are extended to X‐ray‐diffraction‐caught oxodiferric and I‐type peroxodiferric systems from other subunits of the same crystal structure, validating them while determining antiferromagnetic coupling with all such diiron systems except the oxodiferric one. The latter converged, on BS, to ferromagnetic coupling under a wide variety of hybrid DFT functionals and basis sets. The trend of the Heisenberg J coupling reflects and substantiates the structures of the diiron core.

What Makes Inhibitors of BET Proteins Bromodomain Selective? A Case Study with a Lead Candidate for Male Contraceptives

“…QM-MM simulations were set up according to the same methodology previously used for a study with ferritins. [27] Briefly, electrostatic embedding (electrostatic interactions between QM and MM atoms), was carried out according to the original literature, [28] while partial charges on MM atoms surrounding all QM atoms were used to approximate the electrostatic environment where QM atoms are found. In order to maintain the effect of the chemical bond between the MM atom and the QM atom, NAMD code created and placed a hydrogen atom as a link atom along the "broken" QM/MM bond.…”

Drug‐Ribosome Interaction Energies at Site‐E Reveal a Reversed Pattern with Respect to Site‐A, While Showing a Mismatch of Crystal vs. Solution Conformations

“…QM-MM simulations were set up according to the same methodology previously used for a study with ferritins. [14] With the C45 system, the QM region to be treated with either ORCA [15] or MOPAC [16] (Stewart, 2016) software was made to contain G5B, nucleotides G92, C93, C2764, C2765, G2793, G2794, U2795, A2802, Mg 2 + 4186 and a molecule of water that, from MD simulations, had been found in the area of the above residues, for a total of 325 atoms and charge À 6. With the cycloheximide system, the QM region to be treated with MOPAC software was made to contain cycloheximide, nucleotides G92,C 93, A2762, U2763, C2764, G2794, U2795, G2800, A2802, proteins LYS 55, PRO 56, PHE 58 of segname 2P5, Mg + + 3863, and 12 water molecules that, from MD simulations, had been found in the area of the above residues, for a total of 427 atoms and charge À 6.…”

Do Naturally Modified Nucleotides Contribute to Stabilizing Complexes between Ribosomes and Small Molecules? A Case Study with the Antitumor Drug Homoharringtonine

“…QM-MM simulations were set up according to the same methodology previously used for a study with ferritins. [30] Briefly, electrostatic embedding (electrostatic interactions between QM and MM atoms), was carried out according to the original literature, [31] while partial charges on MM atoms surrounding all QM atoms were used to approximate the electrostatic environment where QM atoms are found. With the human ribosome-HHT complex, the QM region to be treated with ORCA software was made to contain, in addition to HHT, nucleotides G3904, A3905, G3907, A4397, C4398, A4449, Ψ4450, G4451, U4452, Ψ4531, as well as 11 TIP3 water molecules.…”