The Journal of Physical Chemistry B最新文献

The microscopic properties and Raman spectra of molten, Li₃AlF₆, Na₃AlF₆, and K₃AlF₆ systems were investigated using first-principles molecular dynamics combined with the Voronoi tessellation method. The results have indicated that Li⁺, Na⁺, and K⁺ exist in a free state, whereas Al³⁺ and F^- form ion clusters ([AlF_x]^3-x) with evidence of free F^- anions. The nature of the alkali metal cation does not significantly affect the average Al-F bond length (1.775 Å). The coordination numbers of Al³⁺ and F^- are 5.22, 5.21, and 4.95 in Li₃AlF₆, Na₃AlF₆ and K₃AlF₆, respectively, indicating a lower content of [AlF₆]^3- and [AlF₅]^2- in K₃AlF₆. The self-diffusion coefficients decrease in the order Li⁺ > Na⁺ > K⁺, and the trend is Na₃AlF₆ > Li₃AlF₆ > K₃AlF₆ for Al³⁺ and F^-. The alkali metal cation has little effect on changes in the atomic charge and spin population of Al³⁺. Single bonds form between Al³⁺ and F^- and exhibit uneven bond order. The upper limits of the HOMO-LUMO gaps for Li₃AlF₆, Na₃AlF₆ and K₃AlF₆ are, 4.82, 2.10, and 3.51 eV, respectively, suggesting higher conductivity of Na₃AlF₆ relative to Li₃AlF₆ and K₃AlF₆ under superheating conditions (40 K above the liquidus temperature).

Misfolding and aggregation of microtubule-associated tau protein is implicated in a variety of neurodegenerative disorders (named tauopathies), including Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). AD is the most common type of dementia associated with aging, and CTE is a special tauopathy that mostly affects contact sports athletes (such as those active in American football and boxing). Experimental studies have found that tau acetylated on residue K353 exhibited a declined aggregation propensity; however, the underlying molecular mechanism remains elusive. In this study, we performed replica exchange and conventional molecular dynamics simulations of acetylated and unacetylated tau protein models in an explicit solvent. Our results revealed that the acetylated R4 (the fourth microtubule-binding repeat domain) dimer showed less β structure and more disordered conformations than the unacetylated one. K353 acetylation weakened peptide-peptide interactions and interrupted the salt-bridge network, thus inhibiting R4 dimerization. Besides, K353 acetylation reduced the β-sheet structure probability and induced loosely packed conformations of R3-R4 (the third and fourth microtubule-binding repeat regions) protofibrils. The replacement of the charged group by acyl on K353 resulted in the loss of K353-D358 salt bridges, leading to the enlargement of the β6-β7 angle and the distance between the carboxyl-terminal and β-turn region, finally eliciting an opened "H" configuration. Our work provided a clear picture of the inhibitory mechanisms of K353 acetylation on tau at the microscopic level, which may be helpful in the development of new therapeutics against tauopathies from the perspective of post-translational modification (PTMs).

Implicit solvation models permit the approximate description of solute-solvent interactions, where water is the most often considered solvent due to its relevance in biological systems. The use of other solvents is less common but is relevant for applications such as in nuclear magnetic resonance (NMR) or chromatography. As an example, chloroform is commonly used in anisotropic NMR to measure residual dipolar couplings (RDCs) of chiral analytes weakly aligned by an alignment medium. They can be calculated from molecular dynamics (MD) simulations with explicit solvent, but it is computationally expensive, because tens of microseconds-long MD trajectories should be collected. Here, we develop a computational protocol and numerical implementation for binding free energies of rigid organic molecules to poly-γ-benzyl-l-glutamate using an implicit solvation model of chloroform. The model parameters are fit to alchemical binding free energies obtained from MD simulations in explicit chloroform and compared to the MD results and another implicit solvation model. Possible applications of the method are docking or Monte Carlo simulations based on a physically meaningful scoring function for the fast prediction of interaction poses of ligands for selective binding or the alignment of analytes.

The rational design of polymers to improve nanorod dispersion and strengthen polymer-nanorod interfacial interactions is crucial for designing nanorod-filled polymer nanocomposites (PNCs). Herein, using coarse-grained molecular dynamics simulations, we studied the effect of polymer chain functionalization on the dispersion state of nanorods, the diffusion/relaxation of polymer matrix chains, and the mechanical properties of the corresponding PNCs. The simulation results showed that the nanorod dispersion state could be adjusted by functionalizing the polymer chain. Enhancing the functionalized bead-nanorod interactions or increasing the polymer chain functionalization degree improved the dispersion state of nanorods. The optimized nanorod dispersion state offered a much larger surface that could interact with the polymer matrix, resulting in an enhanced polymer-nanorod adsorption network. The simulation results indicated that the mechanical properties of the polymer nanocomposites (PNCs) improved progressively with an increase in interactions between functionalized beads and nanorods. However, the improvement was not monotonic with respect to the degree of functionalization, suggesting the existence of an optimal functionalization degree. The underlying mechanism of this was that a higher polymer chain functionalization degree optimized the polymer-nanorod adsorption network but hindered the polymer chain orientation during deformation. This work provides evidence theoretical guidance to design and fabricate nanorod-filled nanocomposites with tailored mechanical properties.

Polysiloxanes are versatile polymeric materials with widespread applications in industries ranging from electronics to biomedical devices because of their unique thermal and viscoelastic properties. Accurate molecular simulations of polysiloxanes are essential for understanding their broad applications from a microscopic perspective. However, the accuracy of these simulations is highly dependent on the quality of the force fields used. In this work, we present a comprehensive benchmark and development of force fields tailored for polydimethylsiloxane, which is one of the most widely used polysiloxane materials. Our focus is on their performance in predicting key thermophysical properties including density, heat capacities, isothermal compressibility, and transport properties such as viscosity and thermal conductivity. Experimental measurements are performed in parallel to rigorously validate simulation outcomes. Existing force fields for polydimethylsiloxane, including those derived for organic and inorganic systems, are systematically evaluated against experimental data to identify limitations in accuracy and transferability. Simulation results are compared extensively with experimental observations across a range of temperatures and pressures, revealing the strengths and shortcomings of these commonly utilized force fields for polydimethylsiloxane. Discrepancies between force field predictions and experimental measurements are analyzed in detail for thermodynamic and transport properties of polydimethylsiloxane. This benchmark study serves as a critical assessment of current force fields for polydimethylsiloxane and offers guidelines for their further development, enabling more reliable simulations of polysiloxane-based materials for various industrial applications.

We compute the potential of mean force (PMF) between semicrystalline polyethylene (PE) nanoplastics (NPLs) and model POPC and DPPC bilayers, which approximate in vivo membranes, using atomistic simulations. Our work shows that atomistic resolution is required to characterize the NPL and lipid interactions. By analyzing the PMF, we demonstrate that the mechanical properties of membranes, rather than NPL semicrystalline morphologies, govern NPL-membrane interactions. Resistance to NPL penetration arises from the elastic energy of the membrane deformation. The flexible POPC membranes resist NPL translocation, and the brittle DPPC membranes fracture under stress. Using an elastic free energy model, we approximate effective repulsions between lipid membranes and NPLs of various sizes. Our mean first-passage time analysis shows that even small, bare NPLs cannot easily penetrate brittle lipid membranes via passive diffusion, even at high concentrations. However, eco-coronas or other mechanisms, such as endocytosis, may still facilitate the cellular uptake of NPLs and MPLs. While semicrystalline morphologies do not directly impact NPL translocation, they do influence NPL behavior within lipid membranes upon translocation. Semicrystalline NPLs remain intact within lipid membranes, whereas amorphous NPLs can dissolve into the hydrophobic core and alter the elastic properties of the membrane.

The 3C-like protease of severe acute respiratory syndrome coronavirus 2, known as the main protease (M^pro), is an attractive drug target for the treatment of coronavirus disease 2019. This study reports the discovery of novel M^pro inhibitors using several in silico techniques, including docking, molecular dynamics (MD), and fragment molecular orbital (FMO) calculations. We performed docking calculations on 5950 compounds with bioactivity, and 12 compounds were selected. An enzymatic assay was conducted, revealing that BP-1-102 exhibits significant M^pro inhibitory activity with an IC₅₀ of 11.1 μM. The identification of seed compounds from the experiments on a few compounds demonstrates the effectiveness of our docking calculations. Furthermore, the detailed analyses using MD and FMO calculations suggested an interaction mechanism in which the hydroxyl group of BP-1-102 forms a hydrogen bond with E166 of M^pro. The M^pro inhibitory activity of SH-4-54, a derivative without the aforementioned hydroxyl group, was investigated and observed to be significantly reduced, with an IC₅₀ of 81.5 μM. This result strongly supports the suggested interaction mechanism.

Since its inception in 2014, Cyrene has emerged as a promising biobased solvent derived from renewable cellulose waste, offering a sustainable alternative to conventional toxic solvents. However, experimental data on its thermodynamic and transport properties remain scarce. This study addresses this critical gap by employing state-of-the-art molecular dynamics simulations. The results provide novel data on Cyrene's phase behavior and fluid dynamics over a wide temperature range (300-700 K) and pressure conditions, including the prediction of critical properties (801 K, 81.04 bar, and 415.389 kg/m³). By leveraging advanced computational techniques, this research elucidates Cyrene's density, diffusion coefficients, and viscosity, with accuracy validated against experimental data where available. These findings enhance our theoretical understanding of Cyrene, supporting its adoption in industrial applications and contributing to the broader agenda of green chemistry. Future work will extend these models to study solvent mixtures and coarse-grained representations, driving further innovation in sustainable solvent design.

A 0.5 molal solution of NaCl in water confined within charged graphene nanoslits represents an intriguing system for molecular dynamics simulation, functioning as a model for a nanocapacitor. This charged configuration not only holds practical significance for the advancement of nanoscale capacitors but also offers valuable insights into how the charged walls and applied electric field influence the structure of water, the movement of ions within the solution, and how these alterations in water impact the overall fluid behavior. The behavior of the solution under nanoconfinement diverges markedly from that observed in bulk conditions, exhibiting distinct structural, dynamic, and dielectric properties. The charging of the graphene nanoslits generates an electric field within the nanopore, which plays a critical role in modulating molecular interactions. Key properties, including the static dielectric constant, polarization, and density of the 0.5 molal solution, are systematically examined through the molecular structure of the confined system. The models employed in this study include the flexible FAB/ϵ model of water, which effectively reproduces various experimental properties of water under different pressure and temperature conditions. Additionally, the NaCl/ϵ model is used, which also captures a range of experimental characteristics associated with sodium chloride solutions. Together, these models facilitate a comprehensive understanding of the complex behavior of water and ions under the influence of nanoconfinement and electric fields, providing insights that are essential for both fundamental science and practical applications in nanotechnology.

In this contribution, we investigate the non-Markovian relaxation dynamics of a vibrating system in contact with a structured environment. Numerical simulations of the vibrational relaxation dynamics of an adsorbate coupled to a bath of phonons are performed using the stochastic multiconfiguration time-dependent Hartree method. Non-Markovian effects arise from the partitioning of the system-bath interaction into explicit and implicit contributions. It is shown that only a small number of explicit bath modes is sufficient to capture the short-time non-Markovian dynamics, and that imposing a "Markovian closure" of the weakly coupled explicit bath allows other physical regimes for the vibrational relaxation dynamics with distinctive signatures to be assessed.