2,197 research outputs found
Effect of stacking interactions on charge transfer states in photoswitches interacting with ion channels
The activity of ion channels can be reversibly photo-controlled via the binding of molecular photoswitches, often based on an azobenzene scaffold. Those azobenzene derivatives interact with aromatic residues of the protein via stacking interactions. In the present work, the effect of face-to-face and t-shaped stacking interactions on the excited state electronic structure of azobenzene and p-diaminoazobenzene integrated into the Na V1.4 channel is computationally investigated. The formation of a charge transfer state, caused by electron transfer from the protein to the photoswitches, is observed. This state is strongly red shifted when the interaction takes place in a face-to-face orientation and electron donating groups are present on the aromatic ring of the amino acids. The low-energy charge transfer state can interfere with the photoisomerization process after excitation to the bright state by leading to the formation of radical species. </p
Sesquicarbene Complexes:Bonding at the Interface Between M-C Single Bonds and M=C Double Bonds
Allylic dimetalated complexes [M2C(vinyl)]+ (M = Au(IPr) and Cr(CO)5 -) incorporate a new coordination mode of carbon. Digold complexes of this type have recently been detected experimentally. The intrinsic bond orbitals, partial charges, and structural parameters of the gold complexes and of chromium analogs were studied computationally and compared to those of the respective monometalated species and hydrocarbons. This showed that such digold complexes have a carbene character at both Au-C bonds comparable to typical carbene complexes of gold. Dichromium complexes with their stronger π-backdonation compete for interaction with carbon's π-orbital; each of the chromium atoms partakes in double bonding that is significant but weaker than that in the carbene analogs. Containing two M-C bonds on the interface between single and double bonds, these bridged complexes can be conceived as "sesquicarbene complexes". The π-system acted in a very adaptive manner and employed additional stabilization of the vinyl system only where needed. Significant carbene character is found simultaneously in both M-C bonds at the same carbon center. The discovery of these complexes with relatively strong double bond character between one carbon and two metal atoms could bring unusual single-carbon-centered organometallic cascade reactions to the horizon
Influence of the Environment on Shaping the Absorption of Monomeric Infrared Fluorescent Proteins
Infrared fluorescent proteins (iRFPs) are potential candidates for deep-tissue in vivo imaging. Here, we provide molecular-level insights into the role of the protein environment in the structural stability of the chromophore within the protein binding pocket through the flexible hydrogen-bonding network using molecular dynamics simulation. Furthermore, we present systematic excited-state analysis to characterize the nature of the first two excited states and the role of the environment in shaping the nature of the chromophore's excited states within the hybrid quantum mechanics/molecular mechanics framework. Our results reveal that the environment red-shifts the absorption of the chromophore by about 0.32 eV compared to the isolated counterpart, and besides the structural stability, the protein environment does not alter the nature of the excited state of the chromophore significantly. Our study contributes to the fundamental understanding of the excited-state processes of iRFPs in a complex environment and provides a design principle for developing iRFPs with desired spectral properties
PySurf:A Framework for Database Accelerated Direct Dynamics
The greatest restriction to the theoretical study of the dynamics of photoinduced processes is computationally expensive electronic structure calculations. Machine learning algorithms have the potential to reduce the number of these computations significantly. Here, PySurf is introduced as an innovative code framework, which is specifically designed for rapid prototyping and development tasks for data science applications in computational chemistry. It comes with powerful Plugin and Workflow engines, which allows intuitive customization for individual tasks. Data is automatically stored through the database framework, which enables additional interpolation of properties in previously evaluated regions of the conformational space. To illustrate the potential of the framework, a code for nonadiabatic surface hopping simulations based on the Landau-Zener algorithm is presented here. Deriving gradients from the interpolated potential energy surfaces allows for full-dimensional nonadiabatic surface hopping simulations using only adiabatic energies (energy only). Simulations of a pyrazine model and ab initio-based calculations of the SO2 molecule show that energy-only calculations with PySurf are able to correctly predict the nonadiabatic dynamics of these prototype systems. The results reveal the degree of sophistication, which can be achieved by the database accelerated energy-only surface hopping simulations being competitive to commonly used semiclassical approaches
HOAX: A Hyperparameter Optimization Algorithm Explorer for Neural Networks
Computational chemistry has become an important tool to predict and
understand molecular properties and reactions. Even though recent years have
seen a significant growth in new algorithms and computational methods that
speed up quantum chemical calculations, the bottleneck for trajectory-based
methods to study photoinduced processes is still the huge number of electronic
structure calculations. In this work, we present an innovative solution, in
which the amount of electronic structure calculations is drastically reduced,
by employing machine learning algorithms and methods borrowed from the realm of
artificial intelligence. However, applying these algorithms effectively
requires finding optimal hyperparameters, which remains a challenge itself.
Here we present an automated user-friendly framework, HOAX, to perform the
hyperparameter optimization for neural networks, which bypasses the need for a
lengthy manual process. The neural network generated potential energy surfaces
(PESs) reduces the computational costs compared to the ab initio-based PESs. We
perform a comparative investigation on the performance of different
hyperparameter optimiziation algorithms, namely grid search, simulated
annealing, genetic algorithm, and bayesian optimizer in finding the optimal
hyperparameters necessary for constructing the well-performing neural network
in order to fit the PESs of small organic molecules. Our results show that this
automated toolkit not only facilitate a straightforward way to perform the
hyperparameter optimization but also the resulting neural networks-based
generated PESs are in reasonable agreement with the ab initio-based PESs.Comment: 18 page
Symmetries and Cluster Synchronization in Multilayer Networks
Real-world systems in epidemiology, social sciences, power transportation,
economics and engineering are often described as multilayer networks. Here we
first define and compute the symmetries of multilayer networks, and then study
the emergence of cluster synchronization in these networks. We distinguish
between independent layer symmetries which occur in one layer and are
independent of the other layers and dependent layer symmetries which involve
nodes in different layers. We study stability of the cluster synchronous
solution by decoupling the problem into a number of independent blocks and
assessing stability of each block through a Master Stability Function. We see
that blocks associated with dependent layer symmetries have a different
structure than the other blocks, which affects the stability of clusters
associated with these symmetries. Finally, we validate the theory in a fully
analog experiment in which seven electronic oscillators of three kinds are
connected with two kinds of coupling
Rural-to-urban migration, socio-economic status and cardiovascular diseases risk factors among Bangladeshi adults : a nationwide population based survey
Background: Rural-to-urban migration is one of the key drivers of urbanization in Bangladesh and may impact on cardiovascular diseases (CVD) risk due to lifestyle changes. This study examined whether CVD risk factors were associated with migration to and duration of urban life, considering socio-economic indicators. Methods: A total of 27,792 participants (18–59 years) from the 2006 Bangladesh cross-sectional Urban Health Survey were included in the analyses of whom 14,167 (M: 7,278; W: 6,889) were non-migrant urban residents and 13,625 (M: 6,413; W: 7,212) were rural-to-urban migrants. Gender-specific prevalence of CVD risk factors were estimated for urban and migrant groups. Multivariate logistic regression models were used to test the association between each CVD risk by education and wealth within each study group and their possible effect modification. An analysis on the rural-to-urban migrant subgroup only was conducted to examine the association between each CVD risk factor and length of urban stay adjusted for demographic and socio-economic indicators. Results: Compared to urban residents, migrants had significantly lower prevalence of overweight/obesity for both genders. Hypertension was higher among urban women while alcohol/illicit drug use was higher among urban men. Mental health disorders were higher among migrants than urban residents for both genders and no difference were noted for diabetes or cigarette smoking prevalence. In both study groups and genders, the risk of overweight/obesity, hypertension and diabetes increased with increasing education and wealth whereas for mental health disorders, alcohol/illicit drug use, cigarette and bidi smoking the reverse was found. Differences in BMI between migrant and urban women were attenuated with increased education levels (p = 0.014 for interaction). Consistent increasing pattern of risk was observed with longer duration of urban stay; in migrant men for obesity (OR = 1.67), smoking (OR = 1.67) and alcohol/illicit drug use (OR = 2.86), and for obesity and mental health disorder among migrant women. Conclusions: Migrants had high proportion of CVD risk factors which were influenced by education, wealth and duration of urban stay
Singlet fission in tetracene:An excited state analysis
Singlet fission is a potential mechanism to enhance the performance of current solar cells. However, the actual mechanism is still a matter of debate, with charge transfer states believed to play an essential role. The probability of the overall process can be related to the electronic coupling between the electronic states. Here, we explore the excited states of three pairs of tetracene with different relative orientation in the crystal structure showing different electronic couplings and identify the role of charge transfer states. First, a suitable theoretical method for the study of the tetracene pairs is determined by comparing time-dependent density functional theory with wave function-based methods in terms of excitation energies, so-called exciton descriptors, and graphical tools such as electron-hole correlation plots and natural transition orbitals. The results show the presence of low-lying charge transfer states in those tetracene pairs with non-zero electronic coupling, suggesting a superexchange-mediated mechanism, and high-lying charge resonance states for the pair with zero electronic coupling. Finally, the lower electron-hole correlation coefficients for pairs with non-zero coupling speak in favour of the superexchange-mediated mechanism, as a weaker Coulombic attraction due to the mixing with charge transfer states further facilitates the formation of the (Formula presented.) state from the photoexcited molecule
Voltage-Gated ion channels: Structure, pharmacology and photopharmacology
Voltage-gated ion channels are transmembrane proteins responsible for the generation and propagation of action potentials in excitable cells. Over the last decade, advancements have enabled the elucidation of crystal structures of ion channels. This progress in structural understanding, particularly in identifying the binding sites of local anesthetics, opens avenues for the design of novel compounds capable of modulating ion conduction. However, many traditional drugs lack selectivity and come with adverse side effects. The emergence of photopharmacology has provided an orthogonal way of controlling the activity of compounds, enabling the regulation of ion conduction with light. In this review, we explore the central pore region of voltage-gated sodium and potassium channels, providing insights from both structural and pharmacological perspectives. We discuss the different binding modes of synthetic compounds that can physically occlude the pore and, therefore, block ion conduction. Moreover, we examine recent advances in the photopharmacology of voltage-gated ion channels, introducing molecular approaches aimed at controlling their activity by using photosensitive drugsPID2020-117806GA-10
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