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Govaniadine, an isoquinoline alkaloid first isolated from Corydalis govaniana Wall., has been reported to possess multiple biological properties. Its potential as a possible dopamine receptor D1 modulator has been assessed in this research work along with its 3D similar structures for hit molecule optimization by in silico methods. Server-based molecular docking calculations were performed to find the best docked pose of the top molecules in terms of binding affinity and total energy. The molecular level details of the ligand molecules interacting with the amino acid residues near the orthosteric site of the dopamine receptor D1 (PDB ID: 7X2F) were elaborated. The stability of the protein-ligand adduct as determined from 200 ns molecular dynamics simulation in terms of structural parameters like root mean square deviation, root mean square fluctuation, radius of gyration, solvent accessible surface area, and hydrogen bond count was reasonable and free energy change from −35.46 ± 2.91 kcal/mol to −16.87 ± 2.91 kcal/mol from molecular mechanics generalized Born surface area method hinted at the spontaneity of the forward reaction for the top molecules. Ligand 626 (PubChem CID: 71109986) could be chosen as a hit candidate with better geometrical and thermodynamic stability and could be a possible modulator. The preliminary results point towards the need for further characterization of govaniadine scaffold-derived hit molecules for their development as effective and safe drug candidates by various experimental and computational techniques.

Hydrogen has been proposed as an important light element in planetary iron cores, while the crystal structure and thermoelasticity of FeHx (x = 1) (FeH hereafter) under inner core conditions remain largely unknown. Recent studies report that FeH adopts an face‐centered cubic (fcc) structure up to core conditions. In this study, using ab initio molecular dynamics, we calculate the free energy and elastic properties of FeH at high P‐T conditions. Our results indicate that the hexagonal close‐packed (hcp) structure of FeHx is favored by both the low hydrogen concentration and the elevated temperature of inner‐core conditions. We also clarify that lattice hydrogen hardens the wave velocities of iron while superionic hydrogen softens it. Both fcc‐ and hcp‐FeH can match inner‐core wave velocities and Poisson's ratio, which supports the hypothesis of hydrogen as a vital light element in the Earth's core. Plain Language Summary: The properties of H‐bearing iron alloys under inner core conditions have been sparsely studied. Here, we calculated the energy difference between face‐centered cubic (fcc) and hexagonal close‐packed (hcp) FeHx as a function of hydrogen concentration at static conditions (T = 0 K). We found that FeHx exhibits hcp structure in H‐poor conditions (x < 0.8) and fcc in H‐rich conditions (x > 0.8) at high pressures. Further Gibbs free energy calculations suggest that the hcp phase is favored at the temperature of Earth's inner core. The inner core hydrogen content was constrained to be ∼0.26–0.34 wt% based on fcc H‐bearing Fe alloy's equations of state. Finally, we calculated the elasticity of FeH (an iron lattice surrounded by superionic hydrogen) and found that the addition of superionic hydrogen dramatically decreased the shear modulus G and shear wave velocities Vs of iron at high temperatures of the inner core. The real core has sound velocities lower than those of pure iron and thus FeHx with superionic hydrogen is a promising core candidate. Key Points: The free energy and thermoelasticity of FeHx were investigated using ab initio molecular dynamics under the Earth's inner core conditionsFeHx adopts an hexagonal close‐packed structure at the high temperatures of the Earth's inner coreSuperionic H can explain the inner core seismic characteristics [ABSTRACT FROM AUTHOR]

The improvement of the solubility of sulfasalazine in physiological media was the major aim of this study. Accordingly, BNNT inspected as a notable candidate for the carriage of this drug in aqueous media. For this purpose, four possible interactions of two tautomer of sulfasalazine with (9,0) boron-nitride nanotube were considered in aqueous media. The compounds were optimized in gas phase using density functional calculations. Solvation free energies and association free energies of the optimized structures were then studied by Monte Carlo simulation and perturbation method in water environment. Outcomes of quantum mechanical calculations presented that interaction of keto form of sulfasalazine produce the most stable complexes with boron-nitride nanotube in gas phase. Simulation results revealed that electrostatic interactions play a vital role in the intermolecular interaction energies after binding of drug and nanotube in aqueous solution. Results of association free energy calculations indicated that complexes of both two sulfasalazine tautomers (keto and enol) and nanotube were stable in solution. Computed solvation free energies in water showed that the interaction with boron-nitride nanotube significantly improved the solubility of sulfasalazine, which could improve its in vivo bioavailability. [ABSTRACT FROM AUTHOR]

Cell responses are usually viewed as transitive events with fixed inputs and outputs that are regulated by feedback loops. In contrast, directed cycles (DCs) have all nodes connected, and the flow is in a single direction. Consequently, DCs can regenerate themselves and implement intransitive logic. DCs are able to couple unrelated chemical reactions to each edge. The output depends upon which node is used as input. DCs can also undergo selection to minimize the loss of thermodynamic entropy while maximizing the gain of information entropy. The intransitive logic underlying DCs enhances their programmability and impacts their evolution. The natural selection of DCs favors the persistence, adaptability, and self-awareness of living organisms and does not depend solely on changes to coding sequences. Rather, the process can be RNA-directed. I use flipons, nucleic acid sequences that change conformation under physiological conditions, as a simple example and then describe more complex DCs. Flipons are often encoded by repeats and greatly increase the Kolmogorov complexity of genomes by adopting alternative structures. Other DCs allow cells to regenerate, recalibrate, reset, repair, and rewrite themselves, going far beyond the capabilities of current computational devices. Unlike Turing machines, cells are not designed to halt but rather to regenerate. [ABSTRACT FROM AUTHOR]

Accurate predictions of ligand binding affinities would greatly accelerate the first stages of drug discovery campaigns. However, using highly accurate interatomic potentials based on quantum mechanics (QM) in free energy methods has been so far largely unfeasible due to their prohibitive computational cost. Here, we present an efficient method to compute QM free energies from simulations using cheap reference potentials, such as force fields (FFs). This task has traditionally been out of reach due to the slow convergence of computing the correction from the FF to theQMpotential. To overcome this bottleneck, we generalize targeted free energy methods to employ multiple maps--implemented with normalizing flow neural networks (NNs)--that maximize the overlap between the distributions. Critically, the method requires neither a separate expensive training phase for the NNs nor samples from the QM potential. We further propose a one-epoch learning policy to efficiently avoid overfitting, and we combine our approach with enhanced sampling strategies to overcome the pervasive problem of poor convergence due to slow degrees of freedom. On the drug-like molecules in the HiPen dataset, the method accelerates the calculation of the free energy difference of switching from an FF to a DFTB3 potential by three orders of magnitude compared to standard free energy perturbation and by a factor of eight compared to previously published nonequilibrium calculations. Our results suggest that our method, in combination with efficient QM/MM calculations, may be used in lead optimization campaigns in drug discovery and to study protein-ligand molecular recognition processes. [ABSTRACT FROM AUTHOR]

Effect of wire diameter and annealing on the properties of internal magnesium diffusion (IMD)-processed MgB 2 composite wires is studied by establishing a correlation with the characteristics of the interfacial reaction zones developed at Mg − B and barrier (Nb) – sheath (Al + Al 2 O 3) interfaces. The MgB 2 superconductor phase grows at the Mg − B interface along with the B-rich MgB 4 phase. Formation of MgB 2 prior to MgB 4 is anticipated owing to a relatively lower Gibbs free energy at annealing temperatures studied. An intermetallic NbAl 3 phase has developed at the barrier – sheath interface whose thickness decreases with an increase in the wire diameter. Development of NbAl 3 further provides mechanical reinforcement and aids at yielding a dense superconductor phase. Resistivity – voltage characteristics of wire indicates the formation of MgB 2 through a huge drop in resistivity values across the core of the wire. An annealing temperature of 645 °C near the melting point of pure Mg (650 °C) and annealing time of 120 min results in highest critical current of the MgB 2 wire. Annealing time beyond 120 min has shown an impediment to the flow current due to crack propagation possibly because of accumulation of stresses within the developed superconductor phase due to grain growth. A significantly greater resistance for the wire with the smallest diameter is attributed to the formation of a thicker NbAl 3 phase. However, highest engineering current density has also been attained by the wire with the smallest diameter annealed at 645 °C for 60 min. [ABSTRACT FROM AUTHOR]

By using the Ginzburg–Landau theory in the nonlinear case, the shape of the inverse domain nucleus in a thin ferroelectric film in a weak electric field is determined. The dependencies of the critical size of the inverse domain nucleus on the film thickness, the strength of external electric field, the temperature and the parameter α s , which determines the polarization pinning at the film planes, are calculated. We have established that when the parameter α s increases above a certain critical value, which depends on film thickness and external field strength, the polarization switches uniformly without domain formation. In the framework of Zeldovich theory of nucleation, the average repolarization velocity has been determined as a function of the film thickness, the external field strength and the parameter α s . [ABSTRACT FROM AUTHOR]

The spleen tyrosine kinase (Syk) plays a pivotal role in immune cells' signal transduction mechanism. While fostamatinib, an FDA-approved Syk inhibitor, is currently used to treat immune thrombocytopenia, the search for improved Syk-targeted medications to treat autoimmune diseases is still underway. Herein, we screened 38,493 compounds against Syk and selected eight leads based on the docking score and ADMET properties, and performed 3 × 200 ns long molecular dynamics simulations of the apo and Syk-ligand complexes. We considered R406, the active component of fostamatinib, as a control. The molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations demonstrated the lead1 ( Δ G b i n d = -30.35 kcal/mol) exhibited a similar binding free energy as the control ( Δ G b i n d = −29.82 kcal/mol). The Syk stabilizing effect of lead1 was also indicated in its network features, sampling space, and residual correlation motion analysis. We further generated 100 structural analogues of lead1 using deep learning, and one of the analogues displayed a better binding free energy ( Δ G b i n d = −47.58 kcal/mol) compared to the control or lead1, facilitated by more favourable van der Waals interactions and lesser binding-opposing net polar forces. This analogue may be further exploited to develop effective therapeutics against Syk-associated diseases after validation in vitro and in vivo. [ABSTRACT FROM AUTHOR]

The influence of a capillary pressure jump in a porous medium on the equilibrium between its liquid and gas phases, defined by the Peng–Robinson equation of state, was investigated. A numerical analysis of the phase diagrams of a gas–condensate mixture, constructed in gas-pressure and liquid-pressure coordinates for different capillary pressure jumps in the mixture, has been performed. The boundary of the two-phase region of such a mixture was determined as a domain of its existence in the two-phase state. The calculations were not associated with a concrete porous medium, and they were based on the condition of phase equilibrium of such a medium at different capillary pressure jumps in it. [ABSTRACT FROM AUTHOR]

Because of the essential role of PLpro in the regulation of replication and dysregulation of the host immune sensing, it is considered a therapeutic target for novel drug development. To reduce the risk of immune evasion and vaccine effectiveness, small molecular therapeutics are the best complementary approach. Hence, we used a structure-based drug-designing approach to identify potential small molecular inhibitors for PLpro of SARS-CoV-2. Initial scoring and re-scoring of the best hits revealed that three compounds NPC320891 (2,2-Dihydroxyindene-1,3-Dione), NPC474594 (Isonarciclasine), and NPC474595 (7-Deoxyisonarciclasine) exhibit higher docking scores than the control GRL0617. Investigation of the binding modes revealed that alongside the essential contacts, i.e., Asp164, Glu167, Tyr264, and Gln269, these molecules also target Lys157 and Tyr268 residues in the active site. Moreover, molecular simulation demonstrated that the reported top hits also possess stable dynamics and structural packing. Furthermore, the residues' flexibility revealed that all the complexes demonstrated higher flexibility in the regions 120–140, 160–180, and 205–215. The 120–140 and 160–180 lie in the finger region of PLpro, which may open/close during the simulation to cover the active site and push the ligand inside. In addition, the total binding free energy was reported to be − 32.65 ± 0.17 kcal/mol for the GRL0617-PLpro, for the NPC320891-PLpro complex, the TBE was − 35.58 ± 0.14 kcal/mol, for the NPC474594-PLpro, the TBE was − 43.72 ± 0.22 kcal/mol, while for NPC474595-PLpro complex, the TBE was calculated to be − 41.61 ± 0.20 kcal/mol, respectively. Clustering of the protein's motion and FEL further revealed that in NPC474594 and NPC474595 complexes, the drug was seen to have moved inside the binding cavity along with the loop in the palm region harboring the catalytic triad, thus justifying the higher binding of these two molecules particularly. In conclusion, the overall results reflect favorable binding of the identified hits strongly than the control drug, thus demanding in vitro and in vivo validation for clinical purposes. [ABSTRACT FROM AUTHOR]

Almost every model of muscle contraction in the literature to date is a molecular power stroke model, even though this corpuscular mechanism is opposed by centuries of science, by 85 years of unrefuted evidence that muscle is a thermodynamic system, and by a quarter century of direct observations that the molecular mechanism of muscle contraction is a molecular switch, not a molecular power stroke. An ensemble of molecular switches is a binary mechanical thermodynamic system from which A.V. Hill's muscle force–velocity relationship is directly derived, where Hill's parameter a is the internal force against which unloaded muscle shortens, and Hill's parameter b is the product of the switch displacement, d, and the actin–myosin ATPase rate. Ignoring this model and the centuries of thermodynamics that preceded it, corpuscularians continue to develop molecular power stroke models, adding to their 65-year jumble of "new", "innovative", and "unconventional" molecular mechanisms for Hill's a and b parameters, none of which resemble the underlying physical chemistry. Remarkably, the corpuscularian community holds the thermodynamicist to account for these discrepancies, which, as outlined here, I have done for 25 years. It is long past time for corpuscularians to be held accountable for their mechanisms, which by all accounts have no foundation in science. The stakes are high. Molecular power stroke models are widely used in research and in clinical decision-making and have, for over half a century, muddied our understanding of the inner workings of one of the most efficient and clean-burning machines on the planet. It is problematic that corpuscularians present these models to stakeholders as science when in fact corpuscularians have been actively defending these models against science for decades. The path forward for scientists is to stop baseless rejections of muscle thermodynamics and to begin testing corpuscular and thermodynamic mechanisms with the goal of disproving one or the other of these hypotheses. [ABSTRACT FROM AUTHOR]

This study explores the potential inhibitory activity of alkaloids, a class of natural compounds isolated from Brazilian biodiversity, against the mJHBP enzyme of the Aedes aegypti mosquito. This mosquito is a significant vector of diseases such as dengue, zika, and chikungunya. The interactions between the ligands and the enzyme at the molecular level were evaluated using computational techniques such as molecular docking, molecular dynamics (MD), and molecular mechanics with generalized Born surface area (MMGBSA) free energy calculation. The findings suggest that these compounds exhibit a high binding affinity with the enzyme, as confirmed by the binding free energies obtained in the simulation. Furthermore, the specific enzyme residues that contribute the most to the stability of the complex with the compounds were identified: specifically, Tyr33, Trp53, Tyr64, and Tyr129. Notably, Tyr129 residues were previously identified as crucial in the enzyme inhibition process. This observation underscores the significance of the research findings and the potential of the evaluated compounds as natural insecticides against Aedes aegypti mosquitoes. These results could stimulate the development of new vector control agents that are more efficient and environmentally friendly. [ABSTRACT FROM AUTHOR]

Gas molecules or weakly interacting molecules are commonly observed to diffuse through and fill space. Therefore, when the molecules initially confined in one compartment are allowed to move through a channel into another empty compartment, we expect that some molecules will be transported into the initially empty compartment. In this work, we thermodynamically analyze this transport process using a simple model consisting of graphene plates, a carbon nanotube (CNT), and nonpolar molecules that are weakly interacting with each other. Specifically, we calculate the free energy change, or the potential of mean force (PMF), as the molecules are transported from one compartment to another compartment. The PMF profile clearly exhibits a global minimum, or a free energy well, at the state wherein the molecules are evenly distributed over the two compartments. To better understand the thermodynamic origin of the well, we calculate the energetic and entropic contributions to the formation of the well, and we show that the entropic change is responsible for it and is the driving force for transport. Our work not only enables a fundamental understanding of the thermodynamic nature of the transport of weakly interacting molecules with molecular details, but also provides a method for calculating the free energy change during transport between two separate spaces connected by a nanochannel. [ABSTRACT FROM AUTHOR]

Understanding the wetting behavior of copper droplet on graphite substrate has important engineering significance for guiding the preparation of Cu/graphite (Cu–C) composite materials. This paper used the molecular dynamics simulation method to analyze the wetting behavior of Cu droplet on the graphite substrate with different Ar pressures at the atomic scale, which ranged from 0 to 3 atm. The molecular dynamics simulation results indicated that for temperatures below 1300 K, Ar pressure hindered the wetting of droplet, while for temperatures above 1300 K, Ar pressure promoted the wetting process of droplet on the graphite substrate. However, in systems with Ar pressure higher than 1.2 atm, the improvement of wetting by Ar pressure no longer increases. In addition, Ar pressures increased the potential of mean force of Cu droplets leaving the graphite substrates, making it more difficult for droplets to detach from the substrates. [ABSTRACT FROM AUTHOR]

We calculate the free energies of adsorption between a solid wall and various arginine derivatives in water using molecular dynamics simulations. We vary the hydrophobic group size of the amino acids in two ways and the hydrophilicity of the solid wall in five ways. The free energy of adsorption decreases by increasing the hydrophilicity of the solid wall, regardless of the size of the hydrophobic group. Amino acids with small hydrophobic groups are adsorbed on the solid wall with the strongest hydrophilicity, but the free energy of the amino acids with large hydrophobic groups is relatively small. The free energy of adsorption in benzene solvent is increased by increasing the hydrophilicity of the solid wall; however, analogous to results in water solvent, it is independent of the size of the hydrophobic group. We attribute these differences in free energy to the effect of solvent molecules localized on the solid wall. Thus, these results may modulate peptide adsorption on a solid surface by the size of the peptide's hydrophobic groups. [ABSTRACT FROM AUTHOR]

• Understanding the factors influencing the stability of transmembrane proteins is important for elucidating their functions. • Related sequence and structure-based parameters with stability of α-helical membrane proteins. • Free energy transfer of hydrophobic peptides, relative contact order, and lipid accessibility are important for stability. • Our method predicts α-helical membrane protein stability with a correlation of 0.89 and mean absolute error of 1.21 kcal/mol. • Developed a webserver for predicting the stability of α-helical membrane proteins. The folding and stability of transmembrane proteins (TMPs) are governed by the insertion of secondary structural elements into the cell membrane followed by their assembly. Understanding the important features that dictate the stability of TMPs is important for elucidating their functions. In this work, we related sequence and structure-based parameters with free energy (ΔG0) of α-helical membrane proteins. Our results showed that the free energy transfer of hydrophobic peptides, relative contact order, total interaction energy, number of hydrogen bonds and lipid accessibility of transmembrane regions are important for stability. Further, we have developed multiple-regression models to predict the stability of α-helical membrane proteins using these features and our method can predict the stability with a correlation and mean absolute error (MAE) of 0.89 and 1.21 kcal/mol, respectively, on jack-knife test. The method was validated with a blind test set of three recently reported experimental ΔG0, which could predict the stability within an average MAE of 0.51 kcal/mol. Further, we developed a webserver for predicting the stability and it is freely available at (https://web.iitm.ac.in/bioinfo2/TMHS/). The importance of selected parameters and limitations are discussed. [ABSTRACT FROM AUTHOR]

In the framework of mean field approximation, we consider a spin system consisting of two interacting sub-ensembles. The intra-ensemble interactions are ferromagnetic, while the inter-ensemble interactions are antiferromagnetic. We define the effective number of the nearest neighbors and show that if the two sub-ensembles have the same effective number of the nearest neighbors, the classical form of critical exponents ( α = 0 , β = 1 / 2 , γ = γ ′ = 1 , δ = 3 ) gives way to the non-classical form ( α = 0 , β = 3 / 2 , γ = γ ′ = 0 , δ = 1 ), and the scaling function changes simultaneously. We demonstrate that this system allows for two second-order phase transitions and two first-order phase transitions. We observe that an external magnetic field does not destroy the phase transitions but only shifts their critical points, allowing for control of the system's parameters. We discuss the regime when the magnetization as a function of the magnetic field develops a low-magnetization plateau and show that the height of this plateau abruptly rises to the value of one when the magnetic field reaches a critical value. Our analytical results are supported by a Monte Carlo simulation of a three-dimensional layered model. [ABSTRACT FROM AUTHOR]

Although originally developed to describe the magnetic behavior of matter, the Ising model represents one of the most widely used physical models, with applications in almost all scientific areas. Even after 100 years, the model still poses challenges and is the subject of active research. In this work, we address the question of whether it is possible to describe the free energy A of a finite-size 2D-Ising model of arbitrary size, based on a couple of analytically solvable 1D-Ising chains. The presented novel approach is based on rigorous statistical-thermodynamic principles and involves modeling the free energy contribution of an added inter-chain bond Δ A bond (β , N) as function of inverse temperature β and lattice size N. The identified simple analytic expression for Δ A bond is fitted to exact results of a series of finite-size quadratic N × N -systems and enables straightforward and instantaneous calculation of thermodynamic quantities of interest, such as free energy and heat capacity for systems of an arbitrary size. This approach is not only interesting from a fundamental perspective with respect to the possible transfer to a 3D-Ising model, but also from an application-driven viewpoint in the context of (Li-ion) batteries where it could be applied to describe intercalation mechanisms. [ABSTRACT FROM AUTHOR]

Titanium dioxide (TiO2) has been proven to be an excellent material for mitigating the continuous impact of elevated carbon dioxide concentrations. Carbon doping has emerged as a promising strategy to enhance the CO2 reduction performance of TiO2. In this study, we investigated the effects of carbon doping on TiO2 using density functional theory (DFT) calculations. Two carbon doping concentrations were considered (4% and 6%), denoted as TiO2-2C and TiO2-3C, respectively. The results showed that after carbon doping, the band gaps of TiO2-2C and TiO2-3C were reduced to 1.58 eV and 1.47 eV, respectively, which is lower than the band gap of pure TiO2 (2.13 eV). This indicates an effective improvement in the electronic structure of TiO2. Barrier energy calculations revealed that compared to pure TiO2 (0.65 eV), TiO2-2C (0.54 eV) and TiO2-3C (0.59 eV) exhibited lower energy barriers, facilitating the transition to *COOH intermediates. These findings provide valuable insights into the electronic structure changes induced by carbon doping in TiO2, which can contribute to the development of sustainable energy and environmental conservation measures to address global climate challenges. [ABSTRACT FROM AUTHOR]

By replacing the internal energy with the free energy, as coordinates in a "space of observables", we slightly modify (the known three) non-holonomic geometrizations from Udriste's et al. work. The coefficients of the curvature tensor field, of the Ricci tensor field, and of the scalar curvature function still remain rational functions. In addition, we define and study a new holonomic Riemannian geometric model associated, in a canonical way, to the Gibbs–Helmholtz equation from Classical Thermodynamics. Using a specific coordinate system, we define a parameterized hypersurface in R 4 as the "graph" of the entropy function. The main geometric invariants of this hypersurface are determined and some of their properties are derived. Using this geometrization, we characterize the equivalence between the Gibbs–Helmholtz entropy and the Boltzmann–Gibbs–Shannon, Tsallis, and Kaniadakis entropies, respectively, by means of three stochastic integral equations. We prove that some specific (infinite) families of normal probability distributions are solutions for these equations. This particular case offers a glimpse of the more general "equivalence problem" between classical entropy and statistical entropy. [ABSTRACT FROM AUTHOR]

In this paper, we consider the one-dimensional Ising model (shortly, 1D-MSIM) having mixed spin- (s , (2 t − 1) / 2)  with the nearest neighbors and the external magnetic field. We establish the partition function of the model using the transfer matrix. We compute certain thermodynamic quantities for the 1D-MSIM. We find some precise formulas to determine the model's free energy, entropy, magnetization, and susceptibility. By examining the iterative equations associated with the model, we use the cavity approach to investigate the phase transition problem. We numerically determine the model's periodicity. [ABSTRACT FROM AUTHOR]

To study whether the free energy principle can explain fetal brain activity and the existence of fetal consciousness via a chaotic dimension derived using artificial intelligence. In this observational study, we used a four-dimensional ultrasound technique obtained to collect images of fetal faces from pregnancies at 27–37 weeks of gestation, between February and December 2021. We developed an artificial intelligence classifier that recognizes fetal facial expressions, which are thought to relate to fetal brain activity. We then applied the classifier to video files of facial images to generate each expression category's probabilities. We calculated the chaotic dimensions from the probability lists, and we created and investigated the free energy principle's mathematical model that was assumed to be linked to the chaotic dimension. We used a Mann–Whitney test, linear regression test, and one-way analysis of variance for statistical analysis. The chaotic dimension revealed that the fetus had dense and sparse states of brain activity, which fluctuated at a statistically significant level. The chaotic dimension and free energy were larger in the sparse state than in the dense state. The fluctuating free energy suggests consciousness seemed to exist in the fetus after 27 weeks. [ABSTRACT FROM AUTHOR]

A direct correlation between the materials property behavior with its associated ferroelectric domain mechanisms and the anisotropic component of the Landau free energy is established for binary PMN‐PT (generation I) and ternary PIN‐PMN‐PT (generation II) relaxor ferroelectric single crystal material systems. In addition to their trade‐off in material properties, the observed ferroelectric domain dynamic and the determined free energy anisotropies, especially as approaching phase transition, provide direct insights into the materials field‐dependent behavior between the binary and ternary ferroelectric systems. Domain configuration features such as lamellar structures in binary PMN‐PT and concentric oval‐like structures in ternary PIN‐PMN‐PT result in different material responses to external stimuli. Compared to binary PMN‐PT, the concentric oval‐like domain structures of ternary PIN‐PMN‐PT result in a 20°C higher temperature range of field‐dependent linear behavior, 40% increase in coercive electric field EC,${E_C},$ higher elastic stiffness during ferroelectric domain switching, and lower electromechanical energy losses. Separation of the isotropic and anisotropic components in the Landau free energy reveals a higher anisotropic free energy contribution from the ternary system, especially at temperature for practical applications. The high anisotropic free energy found in the ternary PIN‐PMN‐PT system implies that the concentric oval‐like domain structure contributes to reduced electromechanical energy losses and enhanced stability under external applied fields. [ABSTRACT FROM AUTHOR]

Leishmania donovani causes the neglected tropical disease visceral leishmaniasis. There is currently no vaccine available to combat the disease. Therefore, chemotherapy is the only treatment option available. However, the available drugs have various adverse effects on the host. As a result, new drugs are needed to treat the disease; natural compounds can be used as an alternative to traditional drugs. This study examined apigenin, diosmin, and naringin as prospective inhibitors against the Leishmania donovani Sterol 24-C- methyltransferase enzyme (LdSMT). All three compounds have a high affinity for the LdSMT and remain stable for 100 ns during the molecular dynamics simulation. In the cell viability assays, these compounds showed excellent IC50 values, with apigenin having the best IC50 value of 16.11 µM against Leishmania donovani promastigote. The findings of this study showed that all three flavonoids could be used as a safe alternative to conventional anti-leishmanial drugs. [ABSTRACT FROM AUTHOR]

In this work we report theoretical calculations of a superconducting island in a strong vortex confinement regime. The obtained results reveal the evolution of the superconducting condensate with an applied magnetic field, depending on the spatial profile of the electron mean-free path in the sample. The results of this study provide an insight about the emergent superconducting properties under such conditions, using the Ginzburg-Landau numerical simulations where spatial variation of thickness of the island and the corresponding variation of the mean free path, omnipresent in similar structures of Pb grown on Si (111), are taken into account. These results offer a new route to tailor superconducting circuits by nanoengineered mean free path, using for example the controlled ion-bombardment on thin films, benefiting from the here shown impact of the spatially-varying mean free path on the vortex distribution, phase of superconducting order parameter, and the critical fields. [ABSTRACT FROM AUTHOR]

The magnetization process of the AA-stacked bilayer honeycomb spin lattice in the out-of-plane applied field is examined in the framework of the Ising model and mean field approximation. Competition between different kinds (antiferromagnetic: AF, or ferromagnetic: FM) of intra-layer and inter-layer spin exchange couplings could lead to the first order magnetization process, characterized by sharp jumps in magnetization curves occurring in critical external fields (spin-flop and spin-flip fields). There is only the spin-flip field at very low temperature and its magnitude depends not only on the intra-layer frustration level but also exchange coupling between spin layers. During the magnetization process, the initial AF bilayer honeycomb spin lattice may undergo ferrimagnetic or week-ferromagnetic states before reaching full ferromagnetic saturation state by the spin-flip field. The results of this work can be applied for an explanation of the spin-flip phenomenon registered in the AF bilayer CrI3. [ABSTRACT FROM AUTHOR]

The SAMPL challenges focus on testing and driving progress of computational methods to help guide pharmaceutical drug discovery. However, assessment of methods for predicting binding affinities is often hampered by computational challenges such as conformational sampling, protonation state uncertainties, variation in test sets selected, and even lack of high quality experimental data. SAMPL blind challenges have thus frequently included a component focusing on host-guest binding, which removes some of these challenges while still focusing on molecular recognition. Here, we report on the results of the SAMPL7 blind prediction challenge for host-guest affinity prediction. In this study, we focused on three different host-guest categories-a familiar deep cavity cavitand series which has been featured in several prior challenges (where we examine binding of a series of guests to two hosts), a new series of cyclodextrin derivatives which are monofunctionalized around the rim to add amino acid-like functionality (where we examine binding of two guests to a series of hosts), and binding of a series of guests to a new acyclic TrimerTrip host which is related to previous cucurbituril hosts. Many predictions used methods based on molecular simulations, and overall success was mixed, though several methods stood out. As in SAMPL6, we find that one strategy for achieving reasonable accuracy here was to make empirical corrections to binding predictions based on previous data for host categories which have been studied well before, though this can be of limited value when new systems are included. Additionally, we found that alchemical free energy methods using the AMOEBA polarizable force field had considerable success for the two host categories in which they participated. The new TrimerTrip system was also found to introduce some sampling problems, because multiple conformations may be relevant to binding and interconvert only slowly. Overall, results in this challenge tentatively suggest that further investigation of polarizable force fields for these challenges may be warranted.

This paper outlines the ways in which Karl Friston’s work illuminates the everyday practice of psychotherapists. These include (a) how the strategic ambiguity of the therapist’s stance brings, via ‘transference’, clients’ priors to light; (b) how the unstructured and negative capability of the therapy session reduces the salience of priors, enabling new top-down models to be forged; (c) how fostering self-reflection provides an additional step in the free energy minimization hierarchy; and (d) how Friston and Frith’s ‘duets for one’ can be conceptualized as a relational zone in which collaborative free energy minimization takes place without sacrificing complexity.

Properties such as lower melting temperature, good tensile strength, good reliability, and well creep resistance, together with low production cost, make the system Bi-Sn an ideal candidate for fine soldering in applications such as reballing or reflow. The first objective of the work was to determine the thermodynamic quantities of Bi and Sn using the electromotive force measurement method in an electrolytic cell (Gibbs’ enthalpies of the mixture, integral molar entropies, and the integral molar excess entropies were determined) at temperatures of 600 K and 903 K. The second objective addressed is the comprehensive characterization of three alloy compositions that were selected and elaborated, namely Bi25Sn75, Bi50Sn50, and Bi75Sn25, and morphological and structural investigations were carried out on them. Optical microscopy and SEM-EDS characterization revealed significant changes in the structure of the elaborated alloys, with all phases being uniformly distributed in the Bi50Sn50 and Bi75Sn25 alloys. These observations were confirmed by XRD and EDP-XRFS analyses. Diffractometric analysis reveals the prevalence of metallic Bi and traces of Sn, the formation of the Sn0.3Bi0.7, Sn0.95Bi0.05 compounds, and SnO and SnO2 phases.

Abstract Hydrogen has been proposed as an important light element in planetary iron cores, while the crystal structure and thermoelasticity of FeHx (x = 1) (FeH hereafter) under inner core conditions remain largely unknown. Recent studies report that FeH adopts an face‐centered cubic (fcc) structure up to core conditions. In this study, using ab initio molecular dynamics, we calculate the free energy and elastic properties of FeH at high P‐T conditions. Our results indicate that the hexagonal close‐packed (hcp) structure of FeHx is favored by both the low hydrogen concentration and the elevated temperature of inner‐core conditions. We also clarify that lattice hydrogen hardens the wave velocities of iron while superionic hydrogen softens it. Both fcc‐ and hcp‐FeH can match inner‐core wave velocities and Poisson's ratio, which supports the hypothesis of hydrogen as a vital light element in the Earth's core.

The growing concerns and cases of COVID-19 with the appearance of novel variants i.e., BA.2.75. BA.5 and XBB have prompted demand for more effective treatment options that could overcome the risk of immune evasion. For this purpose, discovering novel small molecules to inhibit druggable proteins such as PLpro required for viral pathogenesis, replication, survival, and spread is the best choice. Compounds from the Dark chemical matter (DCM) database is consistently active in various screening tests and offer intriguing possibilities for finding drugs that are extremely selective or active against uncommon targets. Considering the essential role of PLpro, the current study uses DCMdatabase for the identification of potential hits using in silico virtual molecular screening and simulation approaches to inhibit the current and emerging variants of SARS-CoV-2. Our results revealed the 10 best compounds with docking scores between −7.99 to −7.03 kcal/mol better than the control drug (GRL0617) among which DC 5977–0726, DC 6623–2024, DC C879-0379 and DC D135-0154 were observed as the best hits. Structural-dynamics properties such as dynamic stability, protein packing, and residue flexibility demonstrated the pharmacologically favorable properties of these top hits in contrast to GRL0617. The hydrogen bonding half-life revealed that Asp164, Arg166, Tyr264, and Tyr268 have major contributions to the hydrogen bonding during the simulation. However, some of the important hydrogen bonds were missing in the control drug (GRL0617). Finally, the total binding free energy was reported to be −34.41 kcal/mol for GRL0617 (control), −41.03 kcal/mol for the DC5977-0726-PLpro, for the DC6623-2024-Plpro complex the TBE was −48.87 kcal/mol, for the for DCC879-0379-Plpro complex the TBE was −45.66 kcal/mol while for the DCD135-0154-PLpro complex the TBE was calculated to be −40.09 kcal/mol respectively, which shows the stronger potency of these compounds against PLpro and further in in vivo and in vitro test are required for the possible usage as potential drug against SARS-CoV-2.

Thermoelectric generators (TEGs) panel is used to produce electrical energy by converting thermal energy into electrical energy depending on the temperature differences (ΔT) between the two sides of the panel, which can generate electrical power over 24 h for different climate conditions (hot, cold, wet or dry). The TEGs panel was designed using Solidworks and the prototype of the TEGs panel was carried out in this study for practical testing and evaluation. The TEGs panel performances and the limitation, including parameters such as power generation, efficiency, response time was studied. In this study, the TEGs panel was exposed to sunlight and cubic ice to consider temperature variations throughout the day. The results showed that the TEGs panel generates electric powers of 8.04437 W and 80.40171 W during the cubic ice and sunlight tests, respectively, for temperature differences (ΔT) of 18 °C and 3.3 °C. The electric power from this test can be used to charge a small mobile phone. It was indicated that the theoretical results by the MATLAB program are closely resemble the laboratory results. Furthermore, the correction ratio for the power of MATLAB validation was 6.59%, while the correction ratio for the efficiency was 5.46%. The response time of the system was ranged from 2 to 6 min, which it is indicating the time needed for the TEGs panel to respond effectively to changes in temperatures. After incorporating the correction ratios from MATLAB simulation, the results showed that the maximum electric power and a maximum efficiency (η) are 57.44 W and 13.5%, respectively, when the temperatures difference (ΔT) reaches 70 °C. This study presents a prototype of a versatile power generator (TEGs panel) offers free energy which can be utilising in insulation of building walls and power generation at the same time.

Thermodynamics is regarded as a universal but not foundational theory because its laws for macroscopic quantities have not been derived from microscopic entities. Thus, to root thermodynamics into the fundamental substance, atomism is revived, thinking that the light quantum is the indivisible and permanent element. Assuming the same basic building blocks constitute everything, the state of any system can be quantified by entropy, the logarithmic probability measure multiplied by Boltzmann's constant. Then, the change in entropy expresses the system's evolution toward thermodynamic balance with its surroundings. These natural processes consuming free energy in the least time accumulate sigmoidally, resulting in skewed distributions found throughout nature. In this way, thermodynamics makes sense of phenomena across disciplines and provides a holistic worldview to address questions such as what the world is, how we know about it, what is the meaning of life and how we should live. This article is part of the theme issue ''Thermodynamics 2.0: Bridging the natural and social sciences (Part 1)'. [ABSTRACT FROM AUTHOR]

We compute the free energy at all temperatures for the spherical pure p-spin models from the generalized Thouless–Anderson–Palmer representation. This is the first example of a mixed p-spin model for which the free energy is computed in the whole replica symmetry breaking phase, without appealing to the famous Parisi formula. [ABSTRACT FROM AUTHOR]

We present a new numerical model describing the transformation of a powder of crystalline particles into a dense poly‐crystalline material. It is based on the key phenomena of sintering: shrinkage and grain coarsening driven by the minimization of the free energy. Representing each grain by a truncated sphere, the model takes into account the complex and changing shape of grains for determining the thermodynamic driving forces and associated kinetic coefficients. We validate the model by comparing the temporal evolution of a system of four particles with that obtained from a mesh‐based method. We performed simulations on polydisperse packings of up to 16,000 particles. Using material and process parameters from the literature, the model accurately reproduces experimental data on the evolution of the grain size distribution for alumina. [ABSTRACT FROM AUTHOR]

The present study tells us about the solubility of DL-α-amino butyric acid (DL-α-Aba) in aqueous binary solvent mixture of sodium sulfate under equilibrium saturated condition through analytical gravimetric method at equidistant temperature. Different thermodynamic factors along with transfer Gibbs energies and entropies under standard condition were estimated by using theoretical methods and by the experimental solubilities. The way of surrounding by solvent molecule of solute amino acid in the said media used through the process and is discussed on the ground of different mode of interactions occurring at the time of solvation. Amino acid (DL-α-Aba) shows more solubility with rising temperature. The study reveals that physical properties of electrolyte (Na2SO4), mixed solvent and the size of the amino acid (DL-α-Aba) molecule are the main governing factors for the chemical stability of solute DL-α-Aba. [ABSTRACT FROM AUTHOR]

Atomic characterization of large nonfibrillar aggregates of amyloid polypeptides cannot be determined by experimental means. Starting from β‐rich aggregates of Y and elongated topologies predicted by coarse‐grained simulations and consisting of more than 100 Aβ16–22 peptides, we performed atomistic molecular dynamics (MD), replica exchange with solute scaling (REST2), and umbrella sampling simulations using the CHARMM36m force field in explicit solvent. Here, we explored the dynamics within 3 μs, the free energy landscape, and the potential of mean force associated with either the unbinding of one single peptide in different configurations within the aggregate or fragmentation events of a large number of peptides. Within the time scale of MD and REST2, we find that the aggregates experience slow global conformational plasticity, and remain essentially random coil though we observe slow beta‐strand structuring with a dominance of antiparallel beta‐sheets over parallel beta‐sheets. Enhanced REST2 simulation is able to capture fragmentation events, and the free energy of fragmentation of a large block of peptides is found to be similar to the free energy associated with fibril depolymerization by one chain for longer Aβ sequences. [ABSTRACT FROM AUTHOR]

To fight against the devastating coronavirus disease 2019 (COVID-19), identifying robust anti-SARS-CoV-2 therapeutics from all possible directions is necessary. To contribute to this effort, we selected a human metabolites database containing waters and lipid-soluble metabolites to screen against the 3-chymotrypsin-like proteases (3CLpro) protein of SARS-CoV-2. The top 8 hits from virtual screening displayed a docking score varying between ~ − 11 and ~ − 14 kcal/mol. Molecular dynamics simulations complement the virtual screening study in conjunction with the molecular mechanics generalized Born surface area (MM/GBSA) scheme. Our analyses revealed that (HMDB0132640) has the best glide docking score, − 14.06 kcal/mol, and MM-GBSA binding free energy, − 18.08 kcal/mol. The other three lead molecules are also selected along with the top molecule through a critical inspection of their pharmacokinetic properties. HMDB0132640 displayed a better binding affinity than the other three compounds (HMDB0127868, HMDB0134119, and HMDB0125821) due to increased favorable contributions from the intermolecular electrostatic and van der Waals interactions. Further, we have investigated the ligand-induced structural dynamics of the main protease. Overall, we have identified new compounds that can serve as potential leads for developing novel antiviral drugs against SARS-CoV-2 and elucidated molecular mechanisms of their binding to the main protease. Identification of probable hits from human metabolites against SARS-CoV-2 using integrated computational approaches-Missed against MS [ABSTRACT FROM AUTHOR]

Water is a key actor of various processes of nature and, therefore, molecular engineering has to take the structural and energetic consequences of hydration into account. While the present review focuses on the target–ligand interactions in drug design, with a focus on biomolecules, these methods and applications can be easily adapted to other fields of the molecular engineering of molecular complexes, including solid hydrates. The review starts with the problems and solutions of the determination of water structures. The experimental approaches and theoretical calculations are summarized, including conceptual classifications. The implementations and applications of water models are featured for the calculation of the binding thermodynamics and computational ligand docking. It is concluded that theoretical approaches not only reproduce or complete experimental water structures, but also provide key information on the contribution of individual water molecules and are indispensable tools in molecular engineering. [ABSTRACT FROM AUTHOR]

CoS2 and FeS2 nanoparticles with mesoporous structures embedded in carbon polyhedrons are prepared by reasonable design of materials (CoS2-FeS2-NC), which are used as a modified cathode material. This composite material can limit the shuttling of polysulfides and catalyze and adsorb polysulfides. Further, electrochemical properties of Li–S batteries are enhanced. Li–S batteries using S/CoS2-FeS2-NC electrodes have the best cycle and rate performance. The S/CoS2-FeS2-NC cathode's initial discharge capacity at 0.2C is 938.9 mAh g–1, while its reversible capacity remains 394.8 mAh g–1 after 200 cycles, with a 0.28% decline on average. S/CoS2-NC and bare sulfur cathodes have maximal discharging capacities of 82.3 and 63.8% of S/CoS2-FeS2-NC cathodes at 0.2C. The initial discharge capacity of S/CoS2-FeS2-NC at 0.5C is 795.6 mAh g–1, and the capacity of 354.4 mAh g–1 is maintained after 200 cycles. So, S/CoS2-FeS2-NC has excellent electrochemical properties. [ABSTRACT FROM AUTHOR]

Microtubules (MTs) are large cytoskeletal polymers, composed of αβ- tubulin heterodimers, capable of stochastically converting from polymerizing to depolymerizing states and vice versa. Depolymerization is coupled with hydrolysis of guanosine triphosphate (GTP) within β- tubulin. Hydrolysis is favored in the MT lattice compared to a free heterodimer with an experimentally observed rate increase of 500- to 700- fold, corresponding to an energetic barrier lowering of 3.8 to 4.0 kcal/mol. Mutagenesis studies have implicated α- tubulin residues, α:E254 and α:D251, as catalytic residues completing the β- tubulin active site of the lower heterodimer in the MT lattice. The mechanism for GTP hydrolysis in the free heterodimer, however, is not understood. Additionally, there has been debate concerning whether the GTP- state lattice is expanded or compacted relative to the GDP state and whether a "compacted" GDP- state lattice is required for hydrolysis. In this work, extensive quantum mechanics/molecular mechanics simulations with transition- tempered metadynamics free- energy sampling of compacted and expanded interdimer complexes, as well as a free heterodimer, have been carried out to provide clear insight into the GTP hydrolysis mechanism. α:E254 was found to be the catalytic residue in a compacted lattice, while in the expanded lattice, disruption of a key salt bridge interaction renders α:E254 less effective. The simulations reveal a barrier decrease of 3.8 ± 0.5 kcal/mol for the compacted lattice compared to a free heterodimer, in good agreement with experimental kinetic measurements. Additionally, the expanded lattice barrier was found to be 6.3 ± 0.5 kcal/mol higher than compacted, demonstrating that GTP hydrolysis is variable with lattice state and slower at the MT tip. [ABSTRACT FROM AUTHOR]

Density functional theory (DFT) and the Møller–Plesset expansion (MP2) calculations were benchmarked to characterize the structure of novel derivatives of carbene hydroxymethylene. In this regard, eleven numbers of primary aldehydes including formaldehyde, acetaldehyde, formyl chloride, 2-chloroacetaldehyde, formyl fluoride, 2-fluoroacetaldehyde, formic acid, propionaldehyde, glyoxal, methyl formate, and formyl bromide (1H–11Br) were scrutinized, at the B3LYP/6-311++G(3d,3p) level of theory. Thereafter, the process of keto-enol tautomerism via a [1,2]-H-shift of 1H–11Br was monitored to reach their corresponding enol forms (1P–11P). For all species (except for one structure), the TS involves a triangle structure of C–O–H and yields cis or trans isomers of a singlet ground-state (S) carbene that contrasts the multiplicity of ordinary carbenes. The bond dissociation energy (BDE) calculations were carried out for the homolytic cleavage of C–H bonds of 1H–11Br. The AIM, as a promising analysis that definitely reveals the nature of the bond, was conducted to characterize the eigenvalues at the bond critical points (BCPs). In addition, the relation between the Hammett equation and thermodynamic parameters was obtained. Our investigation suggests new stable S derivatives of carbene hydroxymethylene that can be isolated. [ABSTRACT FROM AUTHOR]

[Display omitted] • Improving CoPc catalyst performance by identifying potential atomic-style linkers. • Calculations suggest improved CO 2 ERR performance for the NH, PH and S linkers. • Unoccupied spin-down d z 2 orbital components facilitate initial CO 2 adsorption. • Contrary to previous experiments, the NH 2 linker shows weak bonding to CoPc. We investigate the CO 2 electroreduction reaction (CO 2 ERR) using first principles calculations, for the active site tuning of cobalt phthalocyanine (CoPc) via distinct atomic linker species which immobilize CoPc on a carbon nanotube (CNT) substrate. Eight different linker species are studied, along with the effect of linker hydrogenation. Superior reaction performance is predicted for the NH, S and PH linkers, which show activated CO 2 adsorption. This results from spin polarization causing unoccupied d z 2 spin-down states of the cobalt active site at, or above, the Fermi level. Using an 'on-catalyst' reaction scheme, calculated activation barriers for COOH formation and CO desorption are lower for the CoPc-PH-CNT system compared to the CoPc-NH-CNT system and CoPc remains attached to PH-CNT throughout the reaction. We thus expect the PH linker system to have similar or better CO 2 ERR performance compared to the NH and S linker systems but at a slightly higher electrode potential. [ABSTRACT FROM AUTHOR]

The main aim of the study was to assess the acetylcholinesterase-inhibitory potential of triterpenoid saponins (astragalosides) found in the roots of Astragalus mongholicus. For this purpose, the TLC bioautography method was applied and then the IC50 values were calculated for astragalosides II, III and IV (5.9 μM; 4.2 μM, and 4.0 μM, respectively). Moreover, molecular dynamics simulations were carried outto assess the affinity of the tested compounds for POPC and POPG-containing lipid bilayers, which in this case are the models of the blood-brain barrier (BBB). All determined free energy profiles confirmed that astragalosides exhibit great affinity for the lipid bilayer. A good correlation was obtained when comparing the logarithm of n-octanol/water partition coefficient (logPow) lipophilicity descriptor values with the smallest values of free energy of the determined 1D profiles. The affinity for the lipid bilayers changes in the same order as the corresponding logPow values, i.e.,: I > II > III~IV. All compounds exhibit a high and also relatively similar magnitude of binding energies, varying from ca. −55 to −51 kJ/mol. Apositive correlation between the experimentally-determined IC50 values and the theoretically-predicted binding energies expressed by the correlation coefficient value equal 0.956 was observed. [ABSTRACT FROM AUTHOR]

In this paper, we study the equations of nonlinear poroelasticity derived from mixture theory. They describe the quasi-static mechanical behavior of a fluid saturated porous medium. The nonlinearity arises from the compressibility of the fluid and from the dependence of porosity and permeability on the divergence of the displacement. We point some limitations of the model. In our approach, we discretize the quasi-static formulation in time and first consider the corresponding incremental problem. For this, we prove existence of a solution using Brézis’ theory of pseudo-monotone operators. Generalizing Biot’s free energy to the nonlinear setting, we construct a Lyapunov functional, yielding global stability. This allows us to construct bounds that are uniform with respect to the time step. In the case when dissipative interface effects between the fluid and the solid are taken into account, we consider the continuous time case in the limit when the time step tends to zero. This yields existence of a weak free energy solution. [ABSTRACT FROM AUTHOR]