The Journal of Physical Chemistry B最新文献

The molecular origins of ion-channel current-voltage (I-V) relationships are often unclear, obscured by ensemble averaging in experimental analysis and persistent underestimation of single-channel ion currents in simulations. Here, we present a mathematical framework that relates ion channel properties to experimentally measured I-V and current-chemical potential (I-μ) relationships. By accounting for how rates change in response to electrochemical conditions in a multistate kinetic model of systems with sequential binding sites, this approach demonstrates how the spatial arrangement of sites and transition states, together with rate asymmetries in ion uptake, transfer, and release, manifest in distinct open-channel current and conductance profiles. Varying these properties in model systems reveals a molecular basis for understanding rectification and nonohmic open-channel flux. Application to models fit to experimental I-V curves demonstrates that these mechanistic trends hold in heterogeneous systems, suggesting a (potentially) transferable paradigm for open-channel flux in channels and transporters with two or more sequential binding sites. Together, these results establish a theoretical framework for open-channel current and foundation for mechanistically interpreting experimental I-V and I-μ assays.

Gold nanorods (AuNRs) have received considerable attention for their distinctive optical properties and well-defined, low-polydispersity dimensions. These characteristics position them as promising candidates for diverse applications in imaging, sensing, and treating diseases. However, accurate characterization of AuNRs in their native solution state, which is crucial to many applications, presents many challenges─especially if AuNRs are coated with surface layers (e.g., surfactants or grafted polymers). When applied to AuNRs with functionalized surfaces, common techniques such as transmission electron microscopy (TEM), small-angle scattering, and dynamic light scattering (DLS) can present limitations such as small sample sizes, the inability to detect light elements, a lack of a comprehensive analytical framework, and/or a dependence on a priori information about the particle dimensions. In this work, we focus on multiangle depolarized DLS (DDLS) measurements of three distinct, surfactant-coated AuNRs samples in solution. DDLS data was analyzed using two analytical approaches and compared with a genetic algorithm analysis that optimizes the dimensions of the particles to best match relaxation rates obtained from DDLS. For samples that produced high-quality DDLS data, all three approaches yielded length estimates that were highly consistent (within 10-20%) with dimensions obtained from TEM/SEM. In contrast, noisy DDLS data posed challenges for direct analysis, and the genetic algorithm approach emerged as particularly advantageous, providing dimensions that more closely aligned with TEM/SEM values than the analytical methods. Our results suggest that the genetic algorithm can accurately capture the dimensions of the AuNRs from their rotational and translational relaxation rates alone, without the need for additional information (e.g., aspect ratio). Looking to the future, this approach to analyzing DDLS measurements will allow the technique to capture important structural information on more complex, anisotropic nanoparticle systems to enable their use in a wide range of applications.

Chikungunya virus (CHIKV) employs a programmed ribosomal frameshifting element (FSE) to regulate the synthesis of its viral proteins, making the FSE an attractive antiviral target. Yet the structural dynamics that govern its function are complex and poorly understood, with multiple folds discovered. Through computational analysis, we suggest that the FSE's conformation is determined by a competition between thermodynamic stability and cotranslational folding kinetics. Using an integrated computational pipeline, we map the FSE's equilibrium landscape, revealing a thermodynamically favored pseudoknot that emerges only with sufficient flanking residues. We then use kinetic simulations to show that, for the wildtype sequence, this pseudoknot is often kinetically trapped in simpler, less stable stem loop structures that form more rapidly during synthesis. Using this information, we rationally design several mutants to target different folds in the FSE's repertoire. We demonstrate that while a purely thermodynamic design can fail due to kinetic traps, an iterative design procedure, informed by kinetic analysis, can drive the FSE onto a target conformation. Our work explores conformational plasticity and multiple folding pathways of the CHIKV FSE, shows how cotranslational kinetics influence the fold-switching landscapes, establishes a computational framework for kinetic-based RNA engineering, and highlights the importance of considering folding pathways in the design of RNA-targeted therapeutics.

The KRAS G12D mutation is one of the most common oncogenic lesions in human tumors, especially in pancreatic ductal adenocarcinoma. The monobodies 12D1 and 12D5 exhibit high selectivity for the G12D mutant of KRAS compared to the wild-type (WT) form. However, the structural and dynamic factors underlying this specificity are still not fully understood. To explore this, we analyzed the transition direction of conformations, allosteric communication pathways, and residue-residue interaction networks at the protein-protein interface. The G12D mutation causes the switch regions to transition from a closed state to an open state. Binding of 12D1 and 12D5 restores this abnormal transition. Additionally, the G12D mutation disrupts the regular communication pathway from the allosteric site α3 to the switch regions (SW I and SW II) observed in WT KRAS. Binding of 12D1 and 12D5 to the allosteric site restores this communication pathway to its original state. Detailed protein-protein interaction network analyses further reveal that 12D1 and 12D5 form two specific hydrogen bonds with the backbone carboxylate of D12. These hydrogen bonds not only strengthen the hydrophobic contacts at the monobody-KRAS interface but also correct the abnormal conformational equilibrium and restore the disrupted allosteric circuitry. Overall, our findings confirm that D12 is a structurally and functionally validated anchor for the development of next-generation inhibitors targeting G12D KRAS-driven malignancies.

The interaction of water molecules in response to external electric fields plays a crucial role in a wide range of scientific and engineering applications, such as energy conversion, electrochemical systems, environmental remediation, and biomedical processes. Designing and refining these technologies requires an understanding of the molecular scale coupled electro-thermal response of water. In this study, molecular dynamics (MD) simulations on water have been performed to resolve the dielectric and thermal behavior under varying electric fields. Five of the classical MD water models, such as SPC/E, TIP4P, TIP4P/2005, TIP4P/ε, and TIP4P/XAIe, were used to evaluate their performance under varying electric field strengths. The dielectric constant exhibits a nonlinear decline with increasing field, reflecting dipolar saturation; TIP4P/XAIe and TIP4P/ε provide the most accurate responses, while TIP4P shows the largest deviations. Thermal conductivity decreases slightly with field due to restricted molecular rotations, with SPC/E and TIP4P/2005 producing values closest to experiment, though all models overestimate because of their nonpolarizable nature. Self-diffusion remains constant below 0.1 V/Å and declines linearly in higher fields, indicating a reduced molecular mobility. Moreover, unlike older models like TIP4P and SPC/E, recently developed water models (TIP4P/XAIe and TIP4P/ε) exhibit field-induced structural ordering toward ice-like phases and successfully capture electro-freezing transitions, while TIP4P/2005 shows partial electro-freezing behavior. These discoveries offer important insights into the microscopic processes that control the electro-thermal response of water and provide helpful recommendations for the selection and creation of precise water models for modeling electrochemical, energy, and environmental applications.

The liquid crystalline 11OS5 compound, forming the nematic phase and a few smectic phases, is investigated by broadband dielectric spectroscopy and infrared spectroscopy. The dielectric relaxation times, ionic conductivity, and positions of infrared absorption bands corresponding to selected intramolecular vibrations are determined as a function of temperature in the range from an isotropic liquid to a crystal phase. The correlation coefficient matrix and k-means cluster analysis of infrared spectra are tested for detection of phase transitions. The density-functional theory calculations are carried out for interpretation of experimental infrared spectra. The performance of various basis sets and exchange-correlation functionals is compared, including both agreement of scaled calculated band positions with experimental values and computational time. The intermolecular interactions in the crystal phase are inferred from the experimental IR spectra and density-functional theory calculations for dimers in head-to-head and head-to-tail configurations. The experimental temperature dependence of the C═O stretching band suggests that the head-to-tail configuration in the crystal phase is more likely. A significant slowing down of the flip-flop relaxation process is observed at the transition between the smectic C and hexagonal smectic X phases.

The design of functional and sustainable materials requires a detailed understanding of the material properties and degradation mechanisms. In particular, the design of fully biodegradable polymers could allow a quick and controlled decomposition of materials before they accumulate in the environment and break down to micro- and nanoplastics. An important degradation pathway proceeds via the hydrolysis of polyesters. To obtain the best performing material candidates, a multiscale-level understanding that takes into account electronic structure combined with multiple configurations at the macroscopic scale is necessary. In this contribution, we present the extension of the multiscale Quantum Cluster Equilibrium method to oligomer materials. We showcase the first application of this methodology to oligomer systems, in particular oligo(ε-Caprolactone). The ε-Caprolactone oligomers were synthesized and characterized comprehensively by means of NMR, SEC, DSC, and TGA. Experimentally, two melting temperatures were observed, which were predicted by theoretical calculations and are in convincing agreement.

Deuterium-labeled lipids provide a powerful means to probe lipid organization, dynamics, and molecular interactions in complex biological systems. In this work, systematic spectroscopic characterization of deuterated fatty acids, sterols, phospholipids, and sphingolipids using Raman and infrared (IR) spectroscopies is presented. Importantly, this study establishes a fundamental spectroscopic reference framework and analytical guidelines for investigating lipid transformation processes in cells and membranes, as all data presented herein are acquired from well-defined lipid standard compounds. The unique C-D stretching region (2300-2000 cm^-1), located within the spectroscopically "silent" window and absent in endogenous cellular components, was exploited for selective detection and semiquantitative assessment of lipid probes. Integration of C-D band intensities enables the estimation of the probe content in complex matrices as the signal correlates with the degree of deuterium substitution. While the C-D spectral region remained largely invariant with respect to the lipid backbone structure, other vibrational modes, particularly those associated with headgroups or specific functional moieties, exhibited lipid-class-dependent intensity variations upon deuteration, reflecting differences in the molecular environment and vibrational coupling. Importantly, deuteration does not significantly interfere with biological function, as replacing hydrogen with deuterium only marginally increases the atomic mass without altering the chemical structure, polarity, or overall molecular interactions, thereby preserving the native lipid behavior. The reference spectra presented here provide an essential foundation for interpreting hyperspectral vibrational data acquired from cellular and membrane systems, supporting future applications of label-free Raman and IR imaging aimed at monitoring lipid remodeling, metabolic regulation, and therapeutic modulation in biological contexts.

A better understanding of the molecular interactions and, consequently, the structure–property relationships in protic ionic liquids (PIL) can help create more accurate property prediction models and enhance the efficiency of their various applications. This approach is especially relevant in understanding the PIL–H₂O mixtures. Depending on the application, water molecules can be considered as not only an impurity in PILs but also a dopant or even a cosolvent. Our study investigated density, viscosity, electrical conductivity, and derived properties like thermal expansion coefficients, excess molar volume, and excess viscosity of low-toxic alkanolammonium- and carboxylate-based PIL–H₂O mixtures. One- (1D) and two-dimensional (2D) nuclear magnetic resonance spectroscopy was employed to elucidate the distribution of water molecules within the PIL structure. In addition, critical aggregation concentrations (CAC) of PIL–H₂O mixtures were determined based on the physicochemical properties and ¹H longitudinal relaxation times. The results showed that the strength of PIL–H₂O interactions depends on the anion, while the cation affects the position of water in the PIL solvent network. Overall, our study provides valuable insight into the molecular modeling and property prediction of this type of PIL, a promising and currently underexplored subclass of ionic liquids.

Highly alkaline brines comprising mixtures of alkali metal cations are an important component of safe, aqueous chemistries for (long-duration) energy storage, electrowinning for the direct reduction of metal oxides to metal, industrial electrolysis, and many other technological applications. Physicochemical studies of the ion association, solvation dynamics, and transport in this highly concentrated regime are sparse, particularly with LiOH as a mixture component approaching its saturation limit, and could provide key inputs for physics-based modeling efforts and defining operational limits. To this end, this study maps the composition space for KOH/LiOH and KOH/NaOH ranging from total ionic strengths of 1 to 9 M, with a series of alkali cation mixtures at each ionic strength and an emphasis on contrasting the solvation dynamics and transport of brines with Li⁺ cocations versus Na⁺. Combining NMR chemical shift, diffusivity, ionic conductivity, density, viscosity, and NMR relaxation measurements yields a detailed understanding of the hydroxide affinity of Li⁺ compared to K⁺ and Na⁺ as well as the evolution of the solution structure as the Li⁺ saturation limit is approached, culminating in the elucidation of a distinct solvation regime in these mixed cation electrolytes at ionic strengths above 6 M for both KOH/LiOH and KOH/NaOH.