The Journal of Physical Chemistry B最新文献

By tracking temperature-induced changes in vibrational spectra, inelastic neutron scattering revealed how confined water governs the phase behavior of the sodium montmorillonite gels. Translational acoustic phonons hardened (shifted to higher energy), while librational modes softened, corresponding to an increased distortion and confinement of water with decreased water content. For a wet sample (∼166 wt % water content) with well-developed pore structure, vibrational modes underwent a phase change on heating from hexagonal ice-like spectral features to those of bulk-like liquid water near 270 K. For a drier sample hydrated to ∼25 wt %, in which water was confined to the interlayer, only amorphous ice was observed in the vibrational density of states spectra and only a minor phase change occurred below 255 K. Temperature-dependent chemical shifts in the energy transfer of translational and librational modes of ice in frozen sodium montmorillonite were found to be strongly dependent on the size of water-filled pores as influenced by the hydration state.

Block copolymers (BCPs) are exciting materials owing to their ability to self-organize, resulting in ordered mesophases in bulk. A rich variety of interesting novel ordered phases can be obtained by subjecting the polymer to geometrical confinement. In the present study, we investigate the self-assembly behavior of A₂B miktoarm star block copolymer melt under cylindrical and spherical nanopores using self-consistent field theory (SCFT). Compared with the equivalent linear AB diblock copolymer, the A₂B miktoarm star block copolymer tends to influence the phase behavior. The structural frustration and chain conformational entropy loss lead to various ordered phases. The role of introducing an additional arm of the A-block to a linear AB diblock copolymer in phase behavior is examined for the wall selective to the majority component. Under cylindrical confinement, when the two A-arms are in the minority and the surface prefers the B-block, the region of helical phases transitions to the perforated lamella (PL₁) and concentric lamella (CL₁) phases. However, when the A-arms form the majority and prefer the surface, the helical ordering of the minority B-block is favored, and a rich array of ordered phases is obtained, such as single helix (H₁), double helices (H₂), and toroids (T). Similarly, under spherical confinement, when A-arms constitute the majority, interesting morphologies are obtained, such as double helices (H₂), four-hole nanocages (CG₄), a pair of toroids (T₂), a pair of toroids with one sphere (ST₂), and a single toroid flanked by two spheres (ST₁S). Overall, the branched chain architecture of A₂B alters the phase behavior under confinement vis-à-vis the linear AB diblock copolymer.

Protein aggregation into amyloid fibrils underlies numerous human diseases, yet the most widely used fluorescent probe, Thioflavin T (ThT), offers an incomplete picture of the process and fails to detect certain fibril structures. Here, we introduce and characterize the photophysical properties of DANIR-2b(2OH), a water-soluble push-pull dye that overcomes these limitations. It successfully binds early prefibrillar aggregates and small fibrils of the human Islet Amyloid Polypeptide that elude detection by ThT, which we confirm by time-resolved cryo-electron microscopy of aliquots taken during the kinetic assays. We further demonstrate that DANIR-2b(2OH) can also track the aggregation of other amyloid proteins, such as insulin and Aβ_1-42. The protein-dye interaction was characterized via steady-state and time-resolved fluorescent spectroscopy. DANIR-2b(2OH) features environment-sensitive emission, high photostability, and a straightforward synthesis. Critically, it provides a substantially lower noise level in standard plate-reader assays, allowing the tracking of aggregation processes that are not visible in standard ThT measurements. This establishes DANIR-2b(2OH) as a highly sensitive and broadly applicable probe for real-time amyloid aggregation measurements and imaging.

Computer simulations are increasingly significant in drug discovery, especially for predicting ligand affinities through free energy calculations. Absolute alchemical free energy calculations are vital for assessing ligand specificity and selectivity, aiding in differentiating between on-target efficacy and off-target effects. The main challenges in these calculations involve capturing conformational changes in proteins and ligands, predicting binding poses correctly, and modeling molecular interactions using well-parametrized force fields. Here, we evaluate how ab initio derived nonbonded force field parameters predict the specificity among nine BRD4 inhibitors and the selectivity of bromosporine across 22 bromodomains. We replaced nonbonded Open Force Field Sage 2.0.0 parameters with atomic charges, van der Waals radii, and dispersion coefficients obtained from Minimal Basis Iterative Stockholder (D-MBIS) atom partitioning of the polarized electron density, along with incorporating ligand polarization energies. Our ligand force field parameters demonstrated a mean unsigned error of 0.48 kcal/mol in predicting absolute binding free energy for nine BRD4 inhibitors, showing a strong correlation with experimental results. In the bromosporine selectivity set, predictive errors resulted mainly from docking-derived binding poses. By focusing solely on experimentally resolved apo- and holo structures, we accurately replicated experimental selectivity rankings for seven out of eight receptors, identifying those with the highest and lowest binding affinities.

The self-assembly of Tetronics® block copolymers is strongly influenced by additives that modify hydration and interfacial packing within micellar structures. Here, we investigate how octanoic acid (OA) and perfluorooctanoic acid (PFOA) alter the solution behavior of Tetronics® T1304 and T1307 using a combination of cloud point (CP), relative viscosity (η_rel) small-angle neutron scattering (SANS), dynamic light scattering (DLS), transmission electron microscopy (TEM), pyrene fluorescence, and density functional theory (DFT) calculations. In the presence of OA, T1304 exhibits pronounced micellar growth, progressing from spherical to ellipsoidal aggregates and, at higher concentrations, to vesicular structures. These changes arise from OA-induced dehydration of the PEO corona and enhanced packing of PPO domains, as confirmed by increases in aggregation number, low-Q scattering intensity, and a marked decrease in the pyrene I₁/I₃ ratio. In contrast, PFOA produces only modest changes in micellar size while preserving spherical topology over the same concentration range. Although DFT analysis indicates stronger electronic stabilization for Tetronics®-PFOA complexes than for OA, the rigid and lipophobic nature of the fluorocarbon chain limits its ability to penetrate the PPO core and drive curvature changes. The combined experimental and computational results show that additive-induced dehydration and steric compatibility, rather than electronic affinity alone, determine the structural evolution of Tetronics® micelles.

Enzymes use electrostatic interactions to recognize their substrates, preorganize active sites, and stabilize reaction transition states. Formamidopyrimidine-DNA glycosylase (Fpg) is a bacterial enzyme that repairs a pro-mutagenic DNA lesion, 8-oxoguanine; its human homologues are important for cancer prevention. General acid-base catalysis in the active site of Fpg requires a finely tuned proton transfer between Pro1 and Glu2 residues. To assess the protonation state of the active site experimentally, we used EPR spectroscopy with a novel imidazolidine nitroxyl spin label responsive in the physiological pH range. The label showed excellent sensitivity in detecting DNA duplex formation and Fpg binding, allowing us to measure changes in the local electrostatic potential. We constructed DNA duplexes placing the spin label near the active site, as verified by EPR and molecular dynamics. Comparing the pH response of the label bound to wild-type Fpg and its catalytically dead E2Q mutant, we observed a notable deviation at pH 7.00 and above, which provides experimental evidence for a mutation-induced shift in the local electrostatic potential at the spin label site. Thus, our approach allows indirect but sensitive probing of the ionization state of key catalytic residues. This work demonstrates that pH-sensitive spin labels hold great potential for exploring electrostatic interactions in DNA-protein complexes, where fine-tuning of local charge is critical for function.

Understanding how lipid bilayers respond to pressure is essential for interpreting the coupling between membrane proteins and their native environments. Here, we use all-atom molecular dynamics to examine the pressure-temperature behavior of model membranes composed of dimyristoylphosphatidylcholine (DMPC) or its cis-unsaturated analogue Δ9-cis-PC. Within the studied range (288-308 K, 1-2000 bar), DMPC undergoes a liquid-gel transition, while Δ9-cis-PC remains fluid due to unsaturation. The CHARMM36 force field reproduces experimental boundaries with high fidelity: simulated DMPC transitions fall within 5-10 K and 100-300 bar of experimental values, and Δ9-cis-PC exhibits no transition. Hysteresis is modest but most pronounced when starting from low-temperature gels; we propose a split-phase simulation protocol that alleviates the hysteresis problem. We identify the area per lipid, bilayer thickness, and acyl-chain gauche fractions as sensitive phase markers; among these, the gauche fraction provides the most robust signature. Simulations indicate that an interdigitated gel is the equilibrium structure under finite-size conditions, and we propose a novel metric to quantify the extent of this phenomenon. However, at low temperature and high pressure, interdigitation decreases, consistent with the experimental lamellar gel phase. This long-lived interdigitation critically impacts standard order parameters, specifically, area per lipid and membrane thickness. Finally, we discuss in detail how finite-size effects influence phase transition and interdigitation. Overall, these results underscore the accuracy of modern force fields and highlight how simulations are essential to mechanistically complement experimental studies of pressure-sensitive membranes.

This study prepared a composite hydrogel using polyethylene glycol diacrylate (PEGDA) and 2-acrylamido-2-methylpropanesulfonic acid (AMPS) as raw materials, aiming to investigate the relationship between its hydration lubrication mechanism and friction behavior. By adjusting the mass fractions of PEGDA and AMPS, the hydrogel's mechanical properties were matched to those of articular cartilage, achieving a compressive modulus of 3.63 MPa. Friction tests revealed that the hydrogel exhibited a low coefficient of friction, consistently maintained within the range of 0.01-0.03 under various frequencies and load conditions, while demonstrating excellent lubrication stability throughout 7200 cycles of testing. Wetting and swelling tests demonstrate that AMPS effectively enhances the hydrogel's hydrophilicity while suppressing swelling, simultaneously increasing the bound water content within the system. Molecular dynamics simulations validate the excellent compatibility between PEGDA and AMPS. Constrained shear simulations reveal the hydrated lubrication layer's crucial role in mitigating shear stress, dispersing heat dissipation, and maintaining lubrication stability.

The SARS-CoV-2 envelope (E) protein is a small viroporin that drives viral assembly, budding, and host interactions, yet its structural organization has remained elusive. Earlier nuclear magnetic resonance spectroscopy studies hint at oligomerization without direct evidence, and the construct lacks the flexible C-terminal region. To bridge this gap, we synthesized the full-length E protein to investigate its oligomeric state. Using size-exclusion chromatography coupled with multiangle light scattering, we demonstrated that the E protein assembles as a stable pentamer in solution. We then reconstituted the E protein into membrane scaffold protein nanodiscs to mimic the lipid bilayer environment for structural analyses by negative-stain electron microscopy and cryo-electron microscopy, which revealed pentamer-like features. Molecular dynamics simulations of the E protein in a nanodisc and a membrane bilayer setting further corroborated the structural flexibility of the C-terminal domain. Collectively, these data present direct evidence that the SARS-CoV-2 E protein assembles as a pentamer in both solution and membrane-mimetic environments. Our results provide a structural foundation for future investigations into the E protein's roles in ion channel activity, membrane remodeling, and virus-host interactions.

A stable solid electrolyte interphase (SEI), formed by the reductive decomposition of electrolytes at the anode surface, is crucial for ensuring the safety and long-term performance of lithium metal and post-lithium metal batteries. Conventionally, the lowest unoccupied molecular orbital (LUMO) energy of an ion-solvent complex has been used as the primary descriptor for predicting reductive decomposition kinetics and electrolyte stability. In this work, we critically evaluate this assumption and show that LUMO energies do not exhibit a direct linear correlation with reductive decomposition kinetics. Instead, the relationship between LUMO levels and reductive stability is inherently nonlinear across diverse electrolyte chemistries, limiting the general applicability of LUMO-based screening. To address this limitation, we developed machine learning (ML) models that use multiple structural and electronic structure parameters as input features and free energy barriers as the target quantity. The models are trained on free energy barriers obtained from density functional theory (DFT) calculations for 200 ion-solvent complexes spanning a wide range of lithium metal battery (LMB) and post-LMB electrolytes. These nonlinear models were found to significantly outperform traditional linear approaches based solely on the LUMO energy, yielding more accurate predictions of the reductive stability of electrolytes. Our findings highlight the need for multifeature, nonlinear models to capture the complexity of electrolyte reactivity and offer a computational framework to accelerate the rational design of stable electrolytes for next-generation battery technologies.