Examining the origins of observed terahertz modes from an optically pumped atomistic model protein in aqueous solution

The microscopic origins of terahertz (THz) vibrational modes in biological systems are an active and open area of current research. Recent experiments [Physical Review X 8, 031061 (2018)] have revealed the presence of a pronounced mode at $\sim$0.3 THz in fluorophore-decorated bovine serum albumin (BSA) protein in aqueous solution under nonequilibrium conditions induced by optical pumping. This result was heuristically interpreted as a collective elastic fluctuation originating from the activation of a low-frequency phonon mode. In this work, we show that the sub-THz spectroscopic response emerges in a statistically significant manner (> 2$\sigma$) from such collective behavior, illustrating how specific THz vibrational modes can be triggered through optical excitations and other charge reorganization processes. We revisit the theoretical analysis with proof-of-concept molecular dynamics that introduce optical excitations into the simulations. Using information theory techniques, we show that these excitations can induce a multiscale response involving the two optically excited chromophores (tryptophans), other amino acids in the protein, ions, and water. Our results motivate new experiments and fully nonequilibrium simulations to probe these phenomena, as well as the refinement of atomistic models of Fr\"ohlich condensates that are fundamentally determined by nonlinear interactions in biology.Comment: 47 pages in total: consisting of 43 of main manuscipt and 4 pages of supporting informatio

Electron dynamics in complex environments with real-time time dependent density functional theory in a QM-MM framework

This article presents a time dependent density functional theory (TDDFT) implementation to propagate the Kohn-Sham equations in real time, including the effects of a molecular environment through a Quantum-Mechanics Molecular-Mechanics (QM-MM) hamiltonian. The code delivers an all-electron description employing Gaussian basis functions, and incorporates the Amber force-field in the QM-MM treatment. The most expensive parts of the computation, comprising the commutators between the hamiltonian and the density matrix—required to propagate the electron dynamics—, and the evaluation of the exchange-correlation energy, were migrated to the CUDA platform to run on graphics processing units, which remarkably accelerates the performance of the code. The method was validated by reproducing linear-response TDDFT results for the absorption spectra of several molecular species. Two different schemes were tested to propagate the quantum dynamics: (i) a leap-frog Verlet algorithm, and (ii) the Magnus expansion to first-order. These two approaches were confronted, to find that the Magnus scheme is more efficient by a factor of six in small molecules. Interestingly, the presence of iron was found to seriously limitate the length of the integration time step, due to the high frequencies associated with the core-electrons. This highlights the importance of pseudopotentials to alleviate the cost of the propagation of the inner states when heavy nuclei are present. Finally, the methodology was applied to investigate the shifts induced by the chemical environment on the most intense UV absorption bands of two model systems of general relevance: the formamide molecule in water solution, and the carboxy-heme group in Flavohemoglobin. In both cases, shifts of several nanometers are observed, consistently with the available experimental data.Fil: Morzan, Uriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: Ramírez, Francisco Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: Oviedo, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Sanchez, Cristian Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Scherlis Perel, Damian Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: González Lebrero, Mariano Camilo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentin

Vibronic Dynamics of Photodissociating ICN from Simulations of Ultrafast X-Ray Absorption Spectroscopy

Ultrafast UV-pump/soft-X-ray-probe spectroscopy is a subject of great interest since it can provide detailed information about dynamical photochemical processes with ultrafast resolution and atomic specificity. Here, we focus on the photodissociation of ICN in the 1Π1 excited state, with emphasis on the transient response in the soft-X-ray spectral region as described by the ab initio spectral lineshape averaged over the nuclear wavepacket probability density. We find that the carbon K-edge spectral region reveals a rich transient response that provides direct insights into the dynamics of frontier orbitals during the I−CN bond cleavage process. The simulated UV-pump/soft-X-ray-probe spectra exhibit detailed dynamical information, including a time-domain signature for coherent vibration associated with the photogenerated CN fragment. © 2020 The Authors. Published by Wiley-VCH Gmb

Eigenvector Centrality Distribution for Characterization of Protein Allosteric Pathways

Determining the principal energy pathways for allosteric communication in biomolecules, that occur as a result of thermal motion, remains challenging due to the intrinsic complexity of the systems involved. Graph theory provides an approach for making sense of such complexity, where allosteric proteins can be represented as networks of amino acids. In this work, we establish the eigenvector centrality metric in terms of the mutual information, as a mean of elucidating the allosteric mechanism that regulates the enzymatic activity of proteins. Moreover, we propose a strategy to characterize the range of the physical interactions that underlie the allosteric process. In particular, the well known enzyme, imidazol glycerol phosphate synthase (IGPS), is utilized to test the proposed methodology. The eigenvector centrality measurement successfully describes the allosteric pathways of IGPS, and allows to pinpoint key amino acids in terms of their relevance in the momentum transfer process. The resulting insight can be utilized for refining the control of IGPS activity, widening the scope for its engineering. Furthermore, we propose a new centrality metric quantifying the relevance of the surroundings of each residue. In addition, the proposed technique is validated against experimental solution NMR measurements yielding fully consistent results. Overall, the methodologies proposed in the present work constitute a powerful and cost effective strategy to gain insight on the allosteric mechanism of proteins

Short hydrogen bonds enhance nonaromatic protein-related fluorescence.

Fluorescence in biological systems is usually associated with the presence of aromatic groups. Here, by employing a combined experimental and computational approach, we show that specific hydrogen bond networks can significantly affect fluorescence. In particular, we reveal that the single amino acid L-glutamine, by undergoing a chemical transformation leading to the formation of a short hydrogen bond, displays optical properties that are significantly enhanced compared with L-glutamine itself. Ab initio molecular dynamics simulations highlight that these short hydrogen bonds prevent the appearance of a conical intersection between the excited and the ground states and thereby significantly decrease nonradiative transition probabilities. Our findings open the door to the design of new photoactive materials with biophotonic applications

Short hydrogen bonds enhance nonaromatic protein-related fluorescence.

Fluorescence in biological systems is usually associated with the presence of aromatic groups. Here, by employing a combined experimental and computational approach, we show that specific hydrogen bond networks can significantly affect fluorescence. In particular, we reveal that the single amino acid L-glutamine, by undergoing a chemical transformation leading to the formation of a short hydrogen bond, displays optical properties that are significantly enhanced compared with L-glutamine itself. Ab initio molecular dynamics simulations highlight that these short hydrogen bonds prevent the appearance of a conical intersection between the excited and the ground states and thereby significantly decrease nonradiative transition probabilities. Our findings open the door to the design of new photoactive materials with biophotonic applications

Quaternary structure effects on the hexacoordination equilibrium in rice hemoglobin rHb1: Insights from molecular dynamics simulations

Nonsymbiotic hemoglobins (nsHbs) form a widely distributed class of plant proteins, which function remains unknown. Despite the fact that class 1 plant nonsymbiotic hemoglobins are hexacoordinate (6c) heme proteins (hxHbs), their hexacoordination equilibrium constants are much lower than in hxHbs from animals or bacteria. In addition, they are characterized by having very high oxygen affinities and low oxygen dissociation rate constants. Rice hemoglobin 1 (rHb1) is a class 1 nonsymbiotic hemoglobin. It crystallizes as a fully associated homodimer with both subunits in 6c state, but showing slightly different conformations, thus leading to an asymmetric crystallographic homodimer. The residues that constitute the dimeric interface are conserved among all nsHbs, suggesting that the quaternary structure could be relevant to explain the chemical behavior and biological function of this family of proteins. In this work, we analyze the molecular basis that determine the hexacoordination equilibrium in rHb1. Our results indicate that dynamical features of the quaternary structure significantly affect the hexacoordination process. Specifically, we observe that the pentacoordinate state is stabilized in the dimer with respect to the isolated monomers. Moreover, the dimer behaves asymmetrically, in a negative cooperative scheme. The results presented in this work are fully consistent with our previous hypothesis about the key role played by the nature of the CD region in determining the coordination state of globinsFil: Morzan, Uriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires; ArgentinaFil: Capece, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires; ArgentinaFil: Marti, Marcelo Adrian. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires; Argentin

Water Network Dynamics Next to the Oxygen-Evolving Complex of Photosystem II

The influence of the environment on the functionality of the oxygen-evolving complex (OEC) of photosystem II has long been a subject of great interest. In particular, various water channels, which could serve as pathways for substrate water diffusion, or proton translocation, are thought to be critical to catalytic performance of the OEC. Here, we address the dynamical nature of hydrogen bonding along the water channels by performing molecular dynamics (MD) simulations of the OEC and its surrounding protein environment in the S1 and S2 states. Through the eigenvector centrality (EC) analysis, we are able to determine the characteristics of the water network and assign potential functions to the major channels, namely that the narrow and broad channels are likely candidates for proton/water transport, while the large channel may serve as a path for larger ions such as chloride and manganese thought to be essential during PSII assembly

Electron transport in real time from first-principles

While the vast majority of calculations reported on molecular conductance have been based on the static non-equilibrium Green’s function formalism combined with density functional theory (DFT), in recent years a few time-dependent approaches to transport have started to emerge. Among these, the driven Liouville-von Neumann equation [C. G. Sánchez et al., J. Chem. Phys. 124, 214708 (2006)] is a simple and appealing route relying on a tunable rate parameter, which has been explored in the context of semi-empirical methods. In the present study, we adapt this formulation to a density functional theory framework and analyze its performance. In particular, it is implemented in an efficient all-electron DFT code with Gaussian basis functions, suitable for quantum-dynamics simulations of large molecular systems. At variance with the case of the tight-binding calculations reported in the literature, we find that now the initial perturbation to drive the system out of equilibrium plays a fundamental role in the stability of the electron dynamics. The equation of motion used in previous tight-binding implementations with massive electrodes has to be modified to produce a stable and unidirectional current during time propagation in time-dependent DFT simulations using much smaller leads. Moreover, we propose a procedure to get rid of the dependence of the current-voltage curves on the rate parameter. This method is employed to obtain the current-voltage characteristic of saturated and unsaturated hydrocarbons of different lengths, with very promising prospects.Fil: Morzan, Uriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: Ramírez, Francisco Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: González Lebrero, Mariano Camilo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: Scherlis Perel, Damian Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentin

Role of core electrons in quantum dynamics using TDDFT

The explicit simulation of time dependent electronic processes requires computationally onerous routes involving the temporal integration of motion equations for the charge density. Efficiency optimization of these methods typically relies on increasing the integration time-step and on the reduction of the computational cost per step. The implicit representation of inner electrons by effective core potentials-or pseudopotentials-is a standard practice in localized-basis quantum-chemistry implementations to improve the efficiency of ground-state calculations, still preserving the quality of the output. This article presents an investigation on the impact that effective core potentials have on the overall efficiency of real time electron dynamics with TDDFT. Interestingly, the speedups achieved with the use of pseudopotentials in this kind of simulation are on average much more significant than in ground-state calculations, reaching in some cases a factor as large as 600×. This boost in performance originates from two contributions: on the one hand, the size of the density matrix, which is considerably reduced, and, on the other, the elimination of high-frequency electronic modes, responsible for limiting the maximum time-step, which vanish when the core electrons are not propagated explicitly. The latter circumstance allows for significant increases in time-step, that in certain cases may reach up to 3 orders of magnitude, without losing any relevant chemical or spectroscopic information.Fil: Foglia, Nicolás Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: Morzan, Uriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: Scherlis Perel, Damian Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: González Lebrero, Mariano Camilo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentin