Exploring Exact-Factorization-Based Trajectories for Low-Energy Dynamics near a Conical Intersection.

We study low-energy dynamics generated by a two-dimensional two-state Jahn-Teller Hamiltonian in the vicinity of a conical intersection using quantum wave packet and trajectory dynamics. Recently, these dynamics were studied by comparing the adiabatic representation and the exact factorization, with the purpose to highlight the different nature of topological-phase and geometric-phase effects arising in the two theoretical representations of the same problem. Here, we employ the exact factorization to understand how to accurately model low-energy dynamics in the vicinity of a conical intersection using an approximate description of the nuclear motion that uses trajectories. We find that since nonadiabatic effects are weak but non-negligible, the trajectory-based description that invokes the classical approximation struggles to capture the correct behavior.

The metabolic domestication syndrome of budding yeast.

Cellular metabolism evolves through changes in the structure and quantitative states of metabolic networks. Here, we explore the evolutionary dynamics of metabolic states by focusing on the collection of metabolite levels, the metabolome, which captures key aspects of cellular physiology. Using a phylogenetic framework, we profiled metabolites in 27 populations of nine budding yeast species, providing a graduated view of metabolic variation across multiple evolutionary time scales. Metabolite levels evolve more rapidly and independently of changes in the metabolic network's structure, providing complementary information to enzyme repertoire. Although metabolome variation accumulates mainly gradually over time, it is profoundly affected by domestication. We found pervasive signatures of convergent evolution in the metabolomes of independently domesticated clades of Saccharomyces cerevisiae. Such recurring metabolite differences between wild and domesticated populations affect a substantial part of the metabolome, including rewiring of the TCA cycle and several amino acids that influence aroma production, likely reflecting adaptation to human niches. Overall, our work reveals previously unrecognized diversity in central metabolism and the pervasive influence of human-driven selection on metabolite levels in yeasts.

Vibrational Circular Dichroism Spectroscopy with a Classical Polarizable Force Field: Alanine in the Gas and Condensed Phases.

Polarizable force fields are an essential component for the chemically accurate modeling of complex molecular systems with a significant degree of fluxionality, beyond harmonic or perturbative approximations. In this contribution we examine the performance of such an approach for the vibrational spectroscopy of the alanine amino acid, in the gas and condensed phases, from the Fourier transform of appropriate time correlation functions generated along molecular dynamics (MD) trajectories. While the infrared (IR) spectrum only requires the electric dipole moment, the vibrational circular dichroism (VCD) spectrum further requires knowledge of the magnetic dipole moment, for which we provide relevant expressions to be used with polarizable force fields. The AMOEBA force field was employed here to model alanine in the neutral and zwitterionic isolated forms, solvated by water or nitrogen, and as a crystal. Within this framework, comparison of the electric and magnetic dipole moments to those obtained with nuclear velocity perturbation theory based on density-functional theory for the same MD trajectories are found to agree well with one another. The statistical convergence of the IR and VCD spectra is examined and found to be more demanding in the latter case. Comparisons with experimental frequencies are also provided for the condensed phases.

Nonadiabatic dynamics with classical trajectories: The problem of an initial coherent superposition of electronic states.

Advances in coherent light sources and development of pump-probe techniques in recent decades have opened the way to study electronic motion in its natural time scale. When an ultrashort laser pulse interacts with a molecular target, a coherent superposition of electronic states is created and the triggered electron dynamics is coupled to the nuclear motion. A natural and computationally efficient choice to simulate this correlated dynamics is a trajectory-based method where the quantum-mechanical electronic evolution is coupled to a classical-like nuclear dynamics. These methods must approximate the initial correlated electron-nuclear state by associating an initial electronic wavefunction to each classical trajectory in the ensemble. Different possibilities exist that reproduce the initial populations of the exact molecular wavefunction when represented in a basis. We show that different choices yield different dynamics and explore the effect of this choice in Ehrenfest, surface hopping, and exact-factorization-based coupled-trajectory schemes in a one-dimensional two-electronic-state model system that can be solved numerically exactly. This work aims to clarify the problems that standard trajectory-based techniques might have when a coherent superposition of electronic states is created to initialize the dynamics, to discuss what properties and observables are affected by different choices of electronic initial conditions and to point out the importance of quantum-momentum-induced electronic transitions in coupled-trajectory schemes.

Investigating the Photodynamics of trans-Azobenzene with Coupled Trajectories.

In this work, we present the first implementation of coupled-trajectory Tully surface hopping (CT-TSH) suitable for applications to molecular systems. We combine CT-TSH with the semiempirical floating occupation molecular orbital-configuration interaction electronic structure method to investigate the photoisomerization dynamics of trans-azobenzene. Our study shows that CT-TSH can capture correctly decoherence effects in this system, yielding consistent electronic and nuclear dynamics in agreement with (standard) decoherence-corrected TSH. Specifically, CT-TSH is derived from the exact factorization and the electronic coefficients' evolution is directly influenced by the coupling of trajectories, resulting in the improvement of internal consistency if compared to standard TSH.

On the Nature of Geometric and Topological Phases in the Presence of Conical Intersections.

The observable nature of topological phases related to conical intersections in molecules is studied. Topological phases should be ubiquitous in molecular processes, but their elusive character has often made them a topic of discussion. To shed some light on this issue, we simulate the dynamics governed by a Jahn-Teller Hamiltonian and analyze it employing two theoretical representations of the molecular wave function: the adiabatic and the exact factorization. We find fundamental differences between effects related to topological phases arising exclusively in the adiabatic representation, and thus not related to any physical observable, and geometric phases within the exact factorization that can be connected to an observable quantity. We stress that while the topological phase of the adiabatic representation is an intrinsic property of the Hamiltonian, the geometric phase of the exact factorization depends on the dynamics that the system undergoes and is connected to the circulation of the nuclear momentum field.

Significance of Energy Conservation in Coupled-Trajectory Approaches to Nonadiabatic Dynamics.

Through approximating electron-nuclear correlation terms in the exact factorization approach, trajectory-based methods have been derived and successfully applied to the dynamics of a variety of light-induced molecular processes, capturing quantum (de)coherence effects rigorously. These terms account for the coupling among the trajectories, recovering the nonlocal nature of quantum nuclear dynamics that is completely overlooked in traditional independent-trajectory algorithms. Nevertheless, some of the approximations introduced in the derivation of some of these methods do not conserve the total energy. We analyze energy conservation in the coupled-trajectory mixed quantum-classical (CTMQC) algorithm and explore the performance of a modified algorithm, CTMQC-E, where some of the terms are redefined to restore energy conservation. A set of molecular models is used as a test, namely, 2-cis-penta-2,4-dienimium cation, bis(methylene) adamantyl radical cation, butatriene cation, uracil radical cation, and neutral pyrazine.

Influence of the environment on the infrared spectrum of alanine: An effective mode analysis.

The vibrational spectrum of the alanine amino acid was computationally determined in the infrared range 1000-2000 cm-1, under various environments encompassing the gas, hydrated, and crystalline phases, by means of classical molecular dynamics trajectories, carried out with the Atomic Multipole Optimized Energetics for Biomolecular Simulation polarizable force field. An effective mode analysis was performed, in which the spectra are optimally decomposed into different absorption bands arising from well-defined internal modes. In the gas phase, this analysis allows us to unravel the significant differences between the spectra obtained for the neutral and zwitterionic forms of alanine. In condensed phases, the method provides invaluable insight into the molecular origins of the vibrational bands and further shows that peaks with similar positions can be traced to rather different molecular motions.

Inorganic sulfur fixation via a new homocysteine synthase allows yeast cells to cooperatively compensate for methionine auxotrophy.

The assimilation, incorporation, and metabolism of sulfur is a fundamental process across all domains of life, yet how cells deal with varying sulfur availability is not well understood. We studied an unresolved conundrum of sulfur fixation in yeast, in which organosulfur auxotrophy caused by deletion of the homocysteine synthase Met17p is overcome when cells are inoculated at high cell density. In combining the use of self-establishing metabolically cooperating (SeMeCo) communities with proteomic, genetic, and biochemical approaches, we discovered an uncharacterized gene product YLL058Wp, herein named Hydrogen Sulfide Utilizing-1 (HSU1). Hsu1p acts as a homocysteine synthase and allows the cells to substitute for Met17p by reassimilating hydrosulfide ions leaked from met17Δ cells into O-acetyl-homoserine and forming homocysteine. Our results show that cells can cooperate to achieve sulfur fixation, indicating that the collective properties of microbial communities facilitate their basic metabolic capacity to overcome sulfur limitation.

Adiabatic and Nonadiabatic Dynamics with Interacting Quantum Trajectories.

We present a quantum dynamics method based on the propagation of interacting quantum trajectories to describe both adiabatic and nonadiabatic processes within the same formalism. The idea originates from the work of Poirier [Chem. Phys.2010,370, 4-14] and Schiff and Poirier [J. Chem. Phys.2012,136, 031102] on quantum dynamics without wavefunctions. It consists of determining the quantum force arising in the Bohmian hydrodynamic formulation of quantum dynamics using only information about quantum trajectories. The particular time-dependent propagation scheme proposed here results in very stable dynamics. Its performance is discussed by applying the method to analytical potentials in the adiabatic regime, and by combining it with the exact factorization method in the nonadiabatic regime.

Exact Factorization Adventures: A Promising Approach for Non-Bound States.

Modeling the dynamics of non-bound states in molecules requires an accurate description of how electronic motion affects nuclear motion and vice-versa. The exact factorization (XF) approach offers a unique perspective, in that it provides potentials that act on the nuclear subsystem or electronic subsystem, which contain the effects of the coupling to the other subsystem in an exact way. We briefly review the various applications of the XF idea in different realms, and how features of these potentials aid in the interpretation of two different laser-driven dissociation mechanisms. We present a detailed study of the different ways the coupling terms in recently-developed XF-based mixed quantum-classical approximations are evaluated, where either truly coupled trajectories, or auxiliary trajectories that mimic the coupling are used, and discuss their effect in both a surface-hopping framework as well as the rigorously-derived coupled-trajectory mixed quantum-classical approach.

Describing the photo-isomerization of a retinal chromophore model with coupled and quantum trajectories.

The exact factorization of the electron-nuclear wavefunction is applied to the study of photo-isomerization of a retinal chromophore model. We describe such an ultrafast nonadiabatic process by analyzing the time-dependent potentials of the theory and by mimicking nuclear dynamics with quantum and coupled trajectories. The time-dependent vector and scalar potentials are the signature of the exact factorization, as they guide nuclear dynamics by encoding the complete electronic dynamics and including excited-state effects. Analysis of the potentials is, thus, essential-when possible-to predict the time-dependent behavior of the system of interest. In this work, we employ the exact time-dependent potentials, available for the numerically exactly solvable model used here, to propagate quantum nuclear trajectories representing the isomerization reaction of the retinal chromophore. The quantum trajectories are the best possible trajectory-based description of the reaction when using the exact-factorization formalism and, thus, allow us to assess the performance of the coupled-trajectory, fully approximate schemes derived from the exact-factorization equations.

Quantum dynamics with curvilinear coordinates: models and kinetic energy operator.

In order to simplify the numerical solution of the time-dependent or time-independent Schrödinger equations associated with atomic and molecular motions, the use of well-adapted coordinates is essential. Usually, this set of curvilinear coordinates leads to a Hamiltonian operator that is as separable as possible. Although their corresponding kinetic energy operator (KEO) expressions can be derived analytically for small systems or special kinds of coordinates, a numerical and exact approach allows one to compute them in terms of sophisticated curvilinear coordinates. Furthermore, the numerical approach enables one to easily define reduced-dimensionality or constrained models. We present here a recent implementation of this numerical approach that allows nested coordinate transformations, therefore leading to great flexibility in the definition of the curvilinear coordinates. Furthermore, this implementation has no limitations in terms of numbers of atoms or coordinate transformations. The quantum dynamics of the cis-trans photoisomerization of part of the retinal chromophore illustrates the construction of the coordinates and KEO part of a three-dimensional model. This article is part of the theme issue 'Chemistry without the Born-Oppenheimer approximation'.

A Photochemical Reaction in Different Theoretical Representations.

The Born-Oppenheimer picture has forged our representation and interpretation of photochemical processes, from photoexcitation down to the passage through a conical intersection, a funnel connecting different electronic states. In this work, we analyze a full in silico photochemical experiment, from the explicit electronic excitation by a laser pulse to the formation of photoproducts following a nonradiative decay through a conical intersection, by contrasting the picture offered by Born-Oppenheimer and that proposed by the exact factorization. The exact factorization offers an alternative understanding of photochemistry that does not rely on concepts such as electronic states, nonadiabatic couplings, and conical intersections. On the basis of nonadiabatic quantum dynamics performed for a two-state 2D model system, this work allows us to compare Born-Oppenheimer and exact factorization for (i) an explicit photoexcitation with and without the Condon approximation, (ii) the passage of a nuclear wavepacket through a conical intersection, (iii) the formation of excited stationary states in the Franck-Condon region, and (iv) the use of classical and quantum trajectories in the exact factorization picture to capture nonadiabatic processes triggered by a laser pulse.

Nonadiabatic Dynamics with Coupled Trajectories.

In this paper, we discuss coupled-trajectory schemes for molecular-dynamics simulations of excited-state processes. New coupled-trajectory strategies to capture decoherence effects, revival of coherence and nonadiabatic interferences in long-time dynamics are proposed, and compared to independent-trajectory schemes. The working framework is provided by the exact factorization of the electron-nuclear wave function, and it exploits ideas emanating from various surface-hopping schemes. The new coupled-trajectory algorithms are tested on a one-dimensional two-state system using different model parameters which allow one to induce different dynamics. The benchmark is provided by the numerically exact solution of the time-dependent Schrödinger equation.

Electronic Structure and Excited States of the Collision Reaction O(3P) + C2H4: A Multiconfigurational Perspective.

We present a study of the O(3P) + C2H4 scattering reaction, a process that takes place in the interstellar medium and is of relevance in atmospheric chemistry as well. A comprehensive investigation of the electronic properties of the system has been carried out based on multiconfigurational ab initio CASSCF/CASPT2 calculations, using a robust and consistent active space that can deliver accurate potential energy surfaces in the key regions visited by the system. The paper discloses detailed description of the primary reaction pathways and the relevant singlet and triplet excited states at the CASSCF and CASPT2 level, including an accurate description of the critical configurations, such as minima and transition states. The chosen active space and the CASSCF/CASPT2 computational protocol are assessed against coupled-cluster calculations to further check the stability and reliability of the entire multiconfigurational procedure.

Choice of access route for artificial nutrition in cancer patients: 30 y of activity in a home palliative care setting.

OBJECTIVES: Malnutrition negatively affects the quality of life, survival, and clinical outcome of patients with cancer. Home artificial nutrition (HAN) is an appropriate nutritional therapy to prevent death from cachexia and to improve quality of life, and it can be integrated into a home palliative care program. The choice to start home enteral nutrition (HEN) or home parenteral nutrition (HPN) is based on patient-specific indications and contraindications. The aim of this observational study was to analyze the changes that occurred in the criteria for choosing the access route to artificial nutrition during 30 y of activity of a nutritional service team (NST) in a palliative home care setting, as well as to compare indications, clinical nutritional outcomes, and complications between HEN and HPN. METHODS: The following parameters were analyzed and compared for HEN and HPN: tumor site and metastases; nutritional status (body mass index, weight loss in the past 6 mo); basal energy expenditure and oral food intake; Karnofsky performance status; access routes to HEN (feeding tubes) and HPN (central venous catheters); water and protein-calorie support; and survival and complications of HAN. RESULTS: From 1990 to 2020, HAN was started in 1014 patients with cancer (592 men, 422 women; 65.6 ± 12.7 y of age); HPN was started in 666 patients (66%); and HEN was started in 348 patients (34%). At the end of the study, 921 patients had died, 77 had suspended HAN for oral refeeding and 16 were in the progress of HAN. The oral caloric intake was <50% basal energy expenditure in all patients: 721 (71.1%) were unable to eat at all (HEN 270, HPN 451), whereas in 293 patients (28.9%), artificial nutrition was supplementary to oral intake. From 2010 to 2020, the number of central venous catheters for HPN, especially peripherally inserted central catheters, doubled compared with that in the previous 20 y, with a decrease of 71.6% in feeding tubes for HEN. At the beginning, patients on HEN and HPN had comparable nutrition and performance status, and there was no difference in nutritional outcome after 1 mo of HAN. In 215 patients who started supplemental parenteral nutrition to oral feeding, total protein-calorie intake allowed a significant increase in body mass index and Karnofsky performance status. The duration of HEN was longer than that of HPN but was similar to that of supplemental parenteral nutrition. CONCLUSIONS: Over 30 y of nutritional service team activity, the choice of central venous catheters as an access route to HAN increased progressively and significantly due to personalized patient decision-making choices. Nutritional efficacy was comparable between HEN and HPN. In patients who maintained food oral intake, supplemental parenteral nutrition improved weight, performance status, and survival better than other types of HAN.

Quantum-classical nonadiabatic dynamics of Floquet driven systems.

We develop a trajectory-based approach for excited-state molecular dynamics simulations of systems subject to an external periodic drive. We combine the exact-factorization formalism, allowing us to treat electron-nuclear systems in nonadiabatic regimes, with the Floquet formalism for time-periodic processes. The theory is developed starting with the molecular time-dependent Schrödinger equation with the inclusion of an external periodic drive that couples to the system dipole moment. With the support of the Floquet formalism, quantum dynamics is approximated by combining classical-like, trajectory-based, nuclear evolution with electronic dynamics represented in the Floquet basis. The resulting algorithm, which is an extension of the coupled-trajectory mixed quantum-classical scheme for periodically driven systems, is applied to a model study, exactly solvable, with different field intensities.

Multiomics Analysis Provides Insight into the Laboratory Evolution of Escherichia coli toward the Metabolic Usage of Fluorinated Indoles.

Organofluorine compounds are known to be toxic to a broad variety of living beings in different habitats, and chemical fluorination has been historically exploited by mankind for the development of therapeutic drugs or agricultural pesticides. On the other hand, several studies so far have demonstrated that, under appropriate conditions, living systems (in particular bacteria) can tolerate the presence of fluorinated molecules (e.g., amino acids analogues) within their metabolism and even repurpose them as alternative building blocks for the synthesis of cellular macromolecules such as proteins. Understanding the molecular mechanism behind these phenomena would greatly advance approaches to the biotechnological synthesis of recombinant proteins and peptide drugs. However, information about the metabolic effects of long-term exposure of living cells to fluorinated amino acids remains scarce. Hereby, we report the long-term propagation of Escherichia coli (E. coli) in an artificially fluorinated habitat that yielded two strains naturally adapted to live on fluorinated amino acids. In particular, we applied selective pressure to force a tryptophan (Trp)-auxotrophic strain to use either 4- or 5-fluoroindole as essential precursors for the in situ synthesis of Trp analogues, followed by their incorporation in the cellular proteome. We found that full adaptation to both fluorinated Trp analogues requires a low number of genetic mutations but is accompanied by large rearrangements in regulatory networks, membrane integrity, and quality control of protein folding. These findings highlight the cellular mechanisms behind the adaptation to unnatural amino acids and provide the molecular foundation for bioengineering of novel microbial strains for synthetic biology and biotechnology.