Category Archives: Density Functional Theory

Avian cryptochrome 4 binds superoxide

Density Functional Theory, Magnetoreception, Molecular dynamics simulatons

Jean Deviers, Fabien Cailliez, Aurélien de la Lande, Daniel R Kattnig, Comput. Struct. Biol. J. 2024, 26, 11-21. https://doi.org/10.1016/j.csbj.2023.12.009 (open access).

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. The resulting O-containing radical pairs have also been hypothesised to underpin various magnetosensitive traits, but due to fast spin relaxation when tumbling in solution would require immobilisation. We here describe our insights in the binding of superoxide to cryptochrome 4 from C. livia based on extensive all-atom molecular dynamics studies and density-functional theory calculations. The positively charged “crypt” region that leads to the flavin binding pocket transiently binds O at 5 flexible binding sites centred on arginine residues. Typical binding times amounted to tens of nanoseconds, but exceptional binding events extended to several hundreds of nanoseconds and slowed the rotational diffusion, thereby realising rotational correlation times as large as 1 ns. The binding sites are particularly efficient in scavenging superoxide escaping from a putative generation site close to the flavin-cofactor, possibly implying a functional relevance. We discuss our findings in view of a potential magnetosensitivity of biological flavin semiquinone/superoxide radical pairs.

Chlorophyll and pheophytin protonated and deprotonated ions: Observation and theory

Density Functional Theory, hemes and chlorophylls

M Diop, M El-Hayek, J Attard, A Muhieddine, V Veremeienko, S Soorkia, Ph Carbonnière, A de la Lande, B Soep, N Shafizadeh. J. Chem. Phys. 2023, 159, 194308. https://doi.org/10.1063/5.0174351. Link for full text in HAL.

Reproduced with permission from the publisher.

Pheophytin a and chlorophyll a have been investigated by electrospray mass spectrometry in the positive and negative modes, in view of the importance of the knowledge of their properties in photosynthesis. Pheophytin and chlorophyll are both observed intensely in the protonated mode, and their main fragmentation route is the loss of their phytyl chain. Pheophytin is observed intact in the negative mode, while under collisions, it is primarily cleaved beyond the phytyl chain and loses the attaching propionate group. Chlorophyll is not detected in normal conditions in the negative mode, but addition of methanol solvent molecule is detected. Fragmentation of this adduct primarily forms a product (−30 amu) that dissociates into dephytyllated deprotonated chlorophyll. Semi-empirical molecular dynamics calculations show that the phytyl chain is unfolded from the chlorin cycle in pheophytin a and folded in chlorophyll a. Density functional theory calculations have been conducted to locate the charges on protonated and deprotonated pheophytin a and chlorophyll a and have found the major location sites that are notably more stable in energy by more than 0.5 eV than the others. The deprotonation site is found identical for pheophytin a and the chlorophyll a-methanol adduct. This is in line with experiment and calculation locating the addition of methanol on a double bond of deprotonated chlorophyll a.

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

Density Functional Theory, Electron dynamics simulations

Rika Tandiana, Karwan Ali Omar, Eleonora Luppi, Fabien Cailliez, Nguyen-Thi Van-Oanh, Carine Clavaguéra, Aurélien de la Lande. J. Chem. Theor. Comput. 2023, 19, 21, 7740–7752. doi.org/10.1021/acs.jctc.3c00656. Link for full text in HAL.

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. We investigate the ability of Gaussian atomic orbitals (AOC), which were fitted to mimic continuum wave functions, to improve electronic stopping power predictions. AOC are added to standard correlation-consistent basis sets or STO minimal basis sets. Our benchmarks for water irradiation by fast protons clearly advocate for the use of AOC, especially near the Bragg peak. We show that AOC only need to be placed on the molecules struck by the ion. The number of AOC that are added to the usual basis set is relatively small compared to the total number of atomic orbitals, making the use of such a basis set an excellent choice from a computational cost point of view. The optimum basis set combination is applied for the calculation of the stopping power of a proton in water with encouraging agreement with experimental data.

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

Density Functional Theory, Electron dynamics simulations, Methodology, Radiation chemistry

Damien Tolu, Dominique Guillaumont, Aurélien de la Lande. J. Phys. Chem. A. 2023, 127, 34, 7045–7057. doi.org/10.1021/acs.jpca.3c02117. Link to full text in HAL.

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(NO3)4(TBP)2 complex formed in the PUREX process. Electron dynamics is propagated by Real-Time-Dependent Auxiliary Density Functional Theory (RT-TD-ADFT). We investigate the use of previously proposed absorption boundary conditions (ABC) in the molecular orbital space to treat secondary electron emission. Basis set and exchange correlation functional effects with ABC are reported as well as a detailed analysis of the ABC parametrization. Preliminary results on the water molecule and then on TBP show that the phenomenological nature of the ABC parameters necessitates selecting appropriate values for each system under study. Irradiation of free and complexed TBP shows an influence of the ligands on the variation of atomic charges on the femtosecond time scale. An accumulation of atomic charges in the alkyl chains of TBP is observed in the case where the nitrate groups are predominantly irradiated. In addition, we find that the Pu atom regains its electric charge very rapidly after being hit by the projectile, with the coordination sphere serving as an electron reservoir to preserve its formal redox state. This study paves the road toward a full understanding of the degradation of organic extracants employed in the nuclear industry.

Current status of deMon2k for the investigation of the early stages of matter irradiation by time-dependent DFT approaches

Density Functional Theory, Electron dynamics simulations, Methodology, QM/MM, Radiation chemistry, Review

Karwan A Omar, Feven A Korsaye, Rika Tandiana, Damien Tolu, Jean Deviers, Xiaojing Wu, Angela Parise, Aurelio Alvarez-Ibarra, Felix Moncada, Jesus Nain Pedroza-Montero, Daniel Mejía-Rodriguez, Nguyen-Thi Van-Oanh, Fabien Cailliez, Carine Clavaguéra, Karim Hasnaoui, Aurélien de la Lande. Eur. J. Special Topics, 2023. doi.org/10.1140/epjs/s11734-023-00905-6. Full text in HAL.

Special collection: Ultrafast Phenomena from attosecond to picosecond timescales: theory and experiments

We summarize in this article the recent progress made in our laboratories in the development of numerical approaches dedicated to investigating ultrafast physicochemical responses of biological matter subjected to ionizing radiations. Our modules are integrated into the deMon2k software which is a readily available program with highly optimized algorithms for conducting Auxiliary Density Functional Theory (ADFT) calculations. We have developed a computational framework based on Real-Time Time-dependent ADFT to simulate the electronic responses of molecular systems to strong perturbations, while molecular dynamics simulations in the ground and excited states (Ehrenfest dynamics) are available to simulate irradiation-induced ultrafast bond breaking/formation. Constrained ADFT and Multi-component ADFT have also been incorporated to simulate charge transfer processes and nuclear quantum effects, respectively. Finally, a coupling to polarizable force fields further permits to realistically account for the electrostatic effects that the systems’ environment has on the perturbed electron density. The code runs on CPU or hybrid CPU/GPU architectures affording simulations of systems comprised up to 1000 atoms at the DFT level with controlled numerical accuracy. We illustrate the applications of these methodologies by taking results from our recent articles that aimed principally at understanding experimental data from pulse radiolysis experiments.

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

Density Functional Theory, Electron dynamics simulations, Methodology

Feven Alemu Korsaye, Aurélien de la Lande, Ilaria Ciofini. J. Comput. Chem. 2023, 43, 1464. doi.org/10.1002/jcc.26932. Full text in HAL

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 DCT and MACRT 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. The analysis here performed allowed to identify and discard on fly the electronic configurations corresponding to spurious situations.

Ab initio derivation of flavin hyperfine interactions for the protein magnetosensor cryptochrome

Density Functional Theory, Magnetoreception, QM/MM

Jean Deviers, Fabien Cailliez, Bernardo Zúñiga Gutiérrez, Daniel R Kattnig, Aurélien de la Lande. Phys. Chem. Chem. Phys. 2022. 24, 16784-16798. doi.org/10.1039/D1CP05804E. Full text in HAL.

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. Here, we present a comprehensive computational study of the hyperfine couplings in the protonated and unprotonated FAD radicals in cryptochrome 4 from C. livia. We combine long (800 ns) molecular dynamics trajectories to accurate quantum chemistry calculations. Hyperfine parameters are derived using auxiliary density functional theory applied to cluster and hybrid QM/MM (Quantum Mechanics/Molecular Mechanics) models comprising the FAD and its significant surrounding environment, as determined by a detailed sensitivity analysis. Thanks to this protocol we elucidate the sensitivity of the hyperfine interaction parameters to structural fluctuations and the polarisation effect of the protein environment. We find that the ensemble-averaged hyperfine interactions are predominantly governed by thermally induced geometric distortions of the flavin. We discuss our results in view of the expected performance of these radicals as part of a magnetoreceptor. Our data could be used to parametrize spin Hamiltonians including not only average values but also standard deviations.

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

Density Functional Theory, hemes and chlorophylls

Fatemeh Fateminasab, Aurelien de La Lande, Reza Omidyan. RSC Advances, 2022, 12, 4703-4713. doi.org/10.1039/D1RA08398H.

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−1). Also, water hydrogen bonding is quite effective in strengthening the Fe–NO bond in ferrous heme. In contrast in ferric heme, due to the large distance between the H2O and O(NO) and lack of hydrogen bonding, the distal histidine exhibits only a slight effect on the binding of NO to the ferric analogue. Concerning the bond nature of FeII–NO and FeIII–NO in heme, a QTAIM analysis predicts a partially covalent and ionic bond nature in both systems.

Theoretical insights on the effect of environments on binding of CO to the Heme: Ferrous and Ferric systems

Density Functional Theory, hemes and chlorophylls

Fatemeh Fateminasab, Mohammad Aarabi, Aurelien de La Lande, Reza Omidyan. J. Mol. Liquids. 2021, 344, 117961. doi.org/10.1016/j.molliq.2021.117961.

In the present study, we have employed a high-level density functional theory (DFT) model to investigate both implicit and explicit effects of solvation (i.e., the bulk solvation effect as well as microhydration) in addition to the effect of distal Histidine on the binding of CO to Ferrous and Ferric-Heme. It has been predicted that the distal N-methylimidazole (MI) in addition to microsolvation, as a simple mode of environment, leads to a significant stabilization on the binding of CO to Heme-FeII (by ∼ 4 kcal mol−1). This is while no clear alteration has been predicted for the implicit solvation model. For the Ferric heme, and in contrast to the Ferrous system, strong destabilization from the environment has been predicted for binding CO to the Ferric heme analog.

QM/MM with Auxiliary DFT in deMon2k

Density Functional Theory, Methodology, QM/MM

J. D Samaniego-Rojas, L. I. Hernández-Segura, L. López-Sosa, R. I Delgado-Venegas, B. Gomez, J.-C. Lambry, A. de la Lande, T. Mineva, J. Alejandre, B. A Zúñiga-Gutiérrez, R. Flores-Moreno, P. Calaminici, G. Geudtner, A. M Köster.Andreas in Multiscale Dynamics Simulations: Nano and Nano-bio Systems in Complex Environments.Edited by D. Wei and D. R. Salahub. 2021. Royal Chemical Society. doi.org/10.1039/9781839164668-00001

This chapter describes the theoretical background of the quantum mechanical/molecular mechanical (QM/MM) implementation in deMon2k within the framework of auxiliary density functional theory (ADFT). It aims to give the reader an overview of the current state of the art of this QM/MM implementation and perspectives for its future development. To this end, we first derive the ADFT working equations for the QM and QM/MM energy and gradient expressions. Based on the joint QM/MM gradient expression, we present algorithms for QM/MM structure optimizations, transition-state searches and molecular dynamics simulations. The use of auxiliary density perturbation theory (ADPT) in the framework of QM/MM is discussed using illustrative implementations including analytic second-order ADFT energy derivatives, nuclear magnetic resonance chemical shift calculations and excited state calculations using time-dependent ADFT. The chapter closes with the description of a transformation program used to generate deMon2k QM/MM inputs.