Avian cryptochrome 4 binds superoxide.

Flavin-binding cryptochromes are blue-light sensitive photoreceptors that have been implicated with magnetoreception in some species. The photocycle involves an intra-protein photo-reduction of the flavin cofactor, generating a magnetosensitive radical pair, and its subsequent re-oxidation. Superoxide (O) is generated in the re-oxidation with molecular oxygen.

Use of Gaussian-Type Functions for Describing Fast Ion-Matter Irradiation with Time-Dependent Density Functional Theory.

The electronic stopping power is an observable property that quantifies the ability of swift ions to penetrate matter to transfer energy to the electron cloud. The recent literature has proven the value of Real-Time Time-Dependent Density Functional Theory to accurately evaluate this property from first-principles, but questions remain regarding the capability of computer codes relying on atom-centered basis functions to capture the physics at play. In this Perspective, we draw attention to the fact that irradiation by swift ions triggers electron emission into the continuum, especially at the Bragg peak.

Irradiation of Plutonium Tributyl Phosphate Complexes by Ionizing Alpha Particles: A Computational Study.

The PUREX solvent extraction process, widely used for recovering uranium and plutonium from spent nuclear fuel, utilizes an organic solvent composed of tributyl phosphate (TBP). The emission of ionizing particles such as alpha particles, resulting from the decay of plutonium, makes the organic solvent vulnerable to degradation. Here, we study the ultrashort time alpha irradiation of tributylphosphate (TBP) and Pu(NO)(TBP) complex formed in the PUREX process.

On the Role of Charge Transfer in Many-Body Non-Covalent Interactions.

Charge transfer is one of the mechanisms involved in non-covalent interactions. In molecular dimers, its contribution to pairwise interaction energies has been studied extensively using a variety of interaction energy decomposition schemes. In polar interactions such as hydrogen bonds, it can contribute ten or several tens of percent of the interaction energy.

On the Recognition of Natural Substrate CTP and Endogenous Inhibitor ddhCTP of SARS-CoV-2 RNA-Dependent RNA Polymerase: A Molecular Dynamics Study.

The novel coronavirus SARS-CoV-2 is the causative agent of the COVID-19 outbreak that is affecting the entire planet. As the pandemic is still spreading worldwide, with multiple mutations of the virus, it is of interest and of help to employ computational methods for identifying potential inhibitors of the enzymes responsible for viral replication. Attractive antiviral nucleotide analogue RNA-dependent RNA polymerase (RdRp) chain terminator inhibitors are investigated with this purpose.

derivation of flavin hyperfine interactions for the protein magnetosensor cryptochrome.

The radicals derived from flavin adenine dinucleotide (FAD) are a corner stone of recent hypotheses about magnetoreception, including the compass of migratory songbirds. These models attribute a magnetic sense to coherent spin dynamics in radical pairs within the flavo-protein cryptochrome. The primary determinant of sensitivity and directionality of this process are the hyperfine interactions of the involved radicals.

Following the density evolution using real time density functional theory and density based indexes: Application to model push-pull molecules.

Considering as test case a family of organic rod like push-pull molecules, we derived and applied density based index enabling the description and diagnostic of the electronic density evolution in real time-time dependent density functional theory (RT-TDDFT) simulations. In particular, both the charge transfer (CT) distance and a diagnostic index, the D and M respectively, were computed on the fly from the density distribution obtained at a given time and the reference ground state density and their mean values were compared with what obtained at Linear Response-TDDFT level. Besides giving a way of analyzing the density redistribution occurring in time, these tools allowed to show how RT-TDDFT, which is definitely a powerful method to model the evolution of the density in CT or charge separation processes, can be affected by the same artifacts known for LR-TDDFT approaches and, particularly, to those related to the use of approximate exchange correlation functionals.

Insights into the effect of distal histidine and water hydrogen bonding on NO ligation to ferrous and ferric heme: a DFT study.

The effect of distal histidine on ligation of NO to ferrous and ferric-heme, has been investigated with the high-level density functional theoretical (DFT) method. It has been predicted that the distal histidine significantly stabilizes the interaction of NO ferrous-heme (by -2.70 kcal mol).

Anisotropic magnetic field effects in the re-oxidation of cryptochrome in the presence of scavenger radicals.

The avian compass and many other of nature's magnetoreceptive traits are widely ascribed to the protein cryptochrome. There, magnetosensitivity is thought to emerge as the spin dynamics of radicals in the applied magnetic field enters in competition with their recombination. The first and dominant model makes use of a radical pair.

Mechanistic Insights on Heme-to-Heme Transmembrane Electron Transfer Within NADPH Oxydases From Atomistic Simulations.

NOX5 is a member of the NADPH oxidase family which is dedicated to the production of reactive oxygen species. The molecular mechanisms governing transmembrane electron transfer (ET) that permits to shuttle electrons over the biological membrane have remained elusive for a long time. Using computer simulations, we report conformational dynamics of NOX5 embedded within a realistic membrane environment.

First-Principles Simulations of Biological Molecules Subjected to Ionizing Radiation.

Ionizing rays cause damage to genomes, proteins, and signaling pathways that normally regulate cell activity, with harmful consequences such as accelerated aging, tumors, and cancers but also with beneficial effects in the context of radiotherapies. While the great pace of research in the twentieth century led to the identification of the molecular mechanisms for chemical lesions on the building blocks of biomacromolecules, the last two decades have brought renewed questions, for example, regarding the formation of clustered damage or the rich chemistry involving the secondary electrons produced by radiolysis. Radiation chemistry is now meeting attosecond science, providing extraordinary opportunities to unravel the very first stages of biological matter radiolysis.

Elucidating the Electronic Structure of a Delayed Fluorescence Emitter via Orbital Interactions, Excitation Energy Components, Charge-Transfer Numbers, and Vibrational Reorganization Energies.

Recently, Wang and co-workers carried out frontier molecule orbital engineering in the design of -Cz-BNCz, a thermally activated delayed fluorescence (TADF) molecule that emits pure green light at an external quantum efficiency of 27%. To further understand the underlying molecular design principles, we employed four advanced electronic structure analysis tools. First, an absolutely localized molecular orbitals (ALMO-) based analysis indicates an antibonding combination between the highest occupied molecular orbitals (HOMOs) of the donor 3,6-di--butylcarbazole fragment and the acceptor BNCz fragment, which raises the HOMO energy and red-shifts the fluorescence emission wavelength.

The physical stage of radiolysis of solvated DNA by high-energy-transfer particles: insights from new first principles simulations.

The primary processes that occur following direct irradiation of bio-macromolecules by ionizing radiation determine the multiscale responses that lead to biomolecular lesions. The so-called physical stage loosely describes processes of energy deposition and molecular ionization/excitation but remains largely elusive. We propose a new approach based on first principles density functional theory to simulate energy deposition in large and heterogeneous biomolecules by high-energy-transfer particles.

Water binding to Fe hemes studied in a cooled ion trap: characterization of a strong 'weak' ligand.

The interaction of a water molecule with ferric heme-iron protoporphyrin ([PP Fe]) has been investigated in the gas phase in an ion trap and studied theoretically by density functional theory. It is found that the interaction of water with ferric heme leads to a stable [PP-Fe-HO] complex in the intermediate spin state (S = 3/2), in the same state as its unligated [PP-Fe] homologue, without spin crossing during water attachment. Using the Van't Hoff equation, the reaction enthalpy for the formation of a Fe-OH bond has been determined for [PP-Fe-HO] and [PP-Fe-(HO)].

Multicomponent density functional theory with density fitting.

Multicomponent Density Functional Theory (MDFT) is a promising methodology to incorporate nuclear quantum effects, such as zero-point energy or tunneling, or to simulate other types of particles such as muons or positrons using particle densities as basic quantities. As for standard electronic DFT, a still ongoing challenge is to achieve the most efficient implementations. We introduce a multicomponent DFT implementation within the framework of auxiliary DFT, focusing on molecular systems comprising electrons and quantum protons.

Molecular Simulations with in-deMon2k QM/MM, a Tutorial-Review.

deMon2k is a readily available program specialized in Density Functional Theory (DFT) simulations within the framework of Auxiliary DFT. This article is intended as a tutorial-review of the capabilities of the program for molecular simulations involving ground and excited electronic states. The program implements an additive QM/MM (quantum mechanics/molecular mechanics) module relying either on non-polarizable or polarizable force fields.

The dramatic effect of N-methylimidazole on trans axial ligand binding to ferric heme: experiment and theory.

The binding energy of CO, O2 and NO to isolated ferric heme, [FeIIIP]+, was studied in the presence and absence of a σ donor (N-methylimidazole and histidine) as the trans axial ligand. This study combines the experimental determination of binding enthalpies by equilibrium measurements in a low temperature ion trap using the van't Hoff equation and high level DFT calculations. It was found that the presence of N-methylimidazole as the axial ligand on the [FeIIIP]+ porphyrin dramatically weakens the [FeIIIP-ligand]+ bond with an up to sevenfold decrease in binding energy owing to the σ donation by N-methylimidazole to the FeIII(3d) orbitals.

Gating the electron transfer at a monocopper centre through the supramolecular coordination of water molecules within a protein chamber mimic.

Functionality of enzymes is strongly related to water dynamic processes. The control of the redox potential for metallo-enzymes is intimately linked to the mediation of water molecules in the first and second coordination spheres. Here, we report a unique example of supramolecular control of the redox properties of a biomimetic monocopper complex by water molecules.

The surprisingly high ligation energy of CO to ruthenium porphyrins.

A combined theoretical and experimental approach has been used to investigate the binding energy of a ruthenium metalloporphyrin ligated with CO, ruthenium tetraphenylporphyrin [RuII TPP], in the RuII oxidation degree. Measurements performed with VUV ionization using the DESIRS beamline at Synchrotron SOLEIL led to adiabatic ionization energies of [RuII TPP] and its complex with CO, [RuII TPP-CO], of 6.48 ± 0.

AMOEBA Polarizable Force Field Parameters of the Heme Cofactor in Its Ferrous and Ferric Forms.

We report the first parameters of the heme redox cofactors for the polarizable AMOEBA force field in both the ferric and ferrous forms. We consider two types of complexes, one with two histidine side chains as axial ligands and one with a histidine and a methionine side chain as ligands. We have derived permanent multipoles from second-order Møller-Plesset perturbation theory (MP2).

Quantum Chemical Topology of the Electron Localization Function in the Field of Attosecond Electron Dynamics.

We report original analyses of attosecond electron dynamics of molecules subject to collisions by high energy charged particles based on Real-Time Time-Dependent-Density-Functional-Theory simulations coupled to Topological Analyses of the Electron Localization Function (TA-TD-ELF). We investigate irradiation of water and guanine. TA-TD-ELF enables qualitative and quantitative characterizations of bond breaking and formation, of charge migration within topological basins, or of electron attachment to the colliding particle.

Multidimensional Quantum Mechanical Modeling of Electron Transfer and Electronic Coherence in Plant Cryptochromes: The Role of Initial Bath Conditions.

A multidimensional quantum mechanical protocol is used to describe the photoinduced electron transfer and electronic coherence in plant cryptochromes without any semiempirical, e.g., experimentally obtained, parameters.

Ultrafast flavin photoreduction in an oxidized animal (6-4) photolyase through an unconventional tryptophan tetrad.

Photolyases are flavoenzymes repairing UV-induced lesions in DNA, which may be activated by a photoreduction of their FAD cofactor. In most photolyases, this photoreduction proceeds by electron transfer along a chain of three tryptophan (Trp) residues, connecting the flavin to the protein surface. Much less studied, animal (6-4) photolyases (repairing pyrimidine-pyrimidone (6-4) photoproducts) are particularly interesting as they were recently shown to have a longer electron transfer chain, counting four Trp residues.