The Journal of Physical Chemistry B最新文献

PGLa, an antimicrobial peptide (AMP), primarily exerts its antibacterial effects by disrupting bacterial cell membrane integrity. Previous theoretical studies mainly focused on the binding mechanism of PGLa with membranes, while the mechanism of water pore formation induced by PGLa peptides, especially the role of structural flexibility in the process, remains unclear. In this study, using all-atom simulations, we investigated the entire process of membrane deformation caused by the interaction of PGLa with an anionic cell membrane composed of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG). Using a deep learning-based key intermediate identification algorithm, we found that the C-terminal tail plays a crucial role for PGLa insertion into the membrane, and that with its assistance, a variety of water pores formed inside the membrane. Mutation of the tail residues revealed that, in addition to electrostatic and hydrophobic interactions, the flexibility of the tail residues is crucial for peptide insertion and pore formation. The full extension of these flexible residues enhances peptide-peptide and peptide-membrane interactions, guiding the transmembrane movement of PGLa and the aggregation of PGLa monomers within the membrane, ultimately leading to the formation of water-filled pores in the membrane. Overall, this study provides a deep understanding of the transmembrane mechanism of PGLa and similar AMPs, particularly elucidating for the first time the importance of C-terminal flexibility in both insertion and oligomerization processes.

Capillary vibrating sharp-edge spray ionization (cVSSI) has been used to control the droplet charging of nebulized microdroplets and monitor effects on protein ion conformation makeup as determined by mass spectrometry (MS). Here it is observed that the application of voltage results in noticeable differences to the charge state distributions (CSDs) of ubiquitin ions. The data can be described most generally in three distinct voltage regions: Under low-voltage conditions (<+200 V, LV regime), low charge states (2+ to 4+ ions) dominate the mass spectra. For midvoltage conditions (+200 to +600 V, MV regime), higher charge states (7+ to 12+ ions) are observed. For high-voltage conditions (>+600 V, HV regime), the "nano-electrospray ionization (nESI)-type distribution" is achieved in which the 6+ and 5+ species are observed as the dominant ions. Analysis of these results suggests that different pathways to progeny nanodroplet production result in the observed ions. For the LV regime, aerodynamic breakup leads to low charge progeny droplets that are selective for the native solution conformation ensemble of ubiquitin (minus multimeric species). In the MV regime, the large droplets persist for longer periods of time, leading to droplet heating and a shift in the conformation ensemble to partially unfolded species. In the HV regime, droplets access progeny nanodroplets faster, leading to native conformation ensemble sampling as indicated by the observed nESI-type CSD. The notable observation of limited multimer formation and adduct ion formation in the LV regime is hypothesized to result from droplet aero breakup resulting in protein and charge carrier partitioning in sampled progeny droplets. The tunable droplet charging afforded by cVSSI presents opportunities to study the effects of the droplet charge, droplet size, and mass spectrometer inlet temperature on the conformer ensemble sampled by the mass spectrometer. Additionally, the approach may provide a tool for rapid comparison of protein stabilities.

Water is vital to all facets of life and is anomalously behaving in its condensed states, making it continually a substance of interest to researchers. Therefore, attempting to capture its properties via correlations and equations of state is extremely valuable. Liquid water has not been studied as extensively in the low-temperature and high-pressure region as in other regions. Some key applications for correlations in this region are cryopreservation (specifically in certain methods of cryopreservation such as hyperbaric (high-pressure) and isochoric (constant-volume) cryopreservation), deep oceans, hydrospheres, clouds, and precipitation. Although there are not nearly as many models for water at low temperatures and high pressures as there are in other temperature and pressure ranges, there are some models that do currently exist. However, these either do not extend to temperatures and pressures as extreme as the data that exist, or they are complex with large numbers of parameters making them more difficult for application. Herein, we present a new correlation for liquid water valid for the temperature range of 200–300 K (−73–27 °C) and pressure range of 0.1–400 MPa that can analytically calculate volume, isothermal compressibility, isobaric expansivity, constant pressure heat capacity, and speed of sound, using only 17 adjustable parameters. The analytical expressions that we derived, and the fitting method that we used can also be applied to other fluids of interest in the future.

Physical vapor deposition is widely used in the fabrication of organic light-emitting diodes and has the potential to adjust the density and orientation through substrate temperature control, which may lead to enhanced electrical performance. However, it is unclear whether this enhanced property is because of the horizontal molecular orientation or the increased density. The effects of the density and orientation on the electrical properties of a potential electron transport material, (3-dibenzo[c,h]acridin-7-yl)phenyl)diphenylphosphine oxide (TPPO-dibenzacridine), were investigated. According to the gyration tensor analysis, TPPO-dibenzacridine resembled an oblate ellipsoid. Furthermore, these films exhibited the highest density when prepared at a substrate temperature of 87.5% of the glass transition temperature with an increase in density of approximately 1.5%. Variable angle spectroscopic ellipsometry measurements confirmed that the transition dipole moment direction of the dibenzacridine moiety, which is involved in the electrical properties, remained isotropic at this temperature. Although horizontal orientations are known to optimize their π-π overlap and improve the electrical properties, the lowest driving voltage was observed under these conditions, which led to the conclusion that the enhanced electrical properties of TPPO-dibenzacridine are greatly influenced by the increased density rather than by the molecular orientation.

In many simple viruses and virus-like particles, the protein capsid self-assembles around a nucleic-acid genome. Although the assembly process has been studied in detail, relatively little is known about how the capsid disassembles, a potentially important step for infection (in viruses) or cargo delivery (in virus-like particles). We investigate capsid disassembly using a coarse-grained molecular dynamics model of a T = 1 dodecahedral capsid and an RNA-like polymer. We alter the interactions between the subunits of the capsid as well as the ionic strength of the solution to induce partial or complete disassembly of self-assembled particles. We find that disassembly follows nucleation-and-growth kinetics, where the nucleation barrier is related to the interaction strengths as well as to the conformation of the polymer. In particular, we find that polymer segments that interact with adjacent subunits reinforce the subunit-subunit contacts. These results have implications for the design of virus-like particles for applications such as drug delivery. A cargo designed with reinforcement in mind might be used to control the stability of such particles and mediate disassembly.

The antibiotic metronidazole (MNZ) has gained interest as a potential MRI contrast agent for imaging hypoxia. ¹⁵N-labeled MNZ can be efficiently hyperpolarized via SABRE-SHEATH (Signal Amplification By Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei), but the envisioned MRI approach requires that MNZ rapidly undergoes structural changes in hypoxic environments with significant ¹⁵N frequency differences manifested in its downstream metabolic products. We have performed NMR studies of the anticipated metabolic product amino-MNZ (despite anticipated stability concerns) accompanied by computational density functional theory (DFT) studies to predict the ¹⁵N chemical shifts of different relevant species. Direct hyperpolarization of sparse naturally abundant ¹⁵N spins in amino-MNZ via SABRE-SHEATH (enhancement up to ∼9400 fold), along with ¹H-decoupled ¹⁵N NMR, allowed comparison with both ¹⁵N₃-MNZ and naturally abundant MNZ. The results show significant ¹⁵N shift differences that agree with the DFT predictions. Taken together, the results show that it should be possible to readily distinguish the parent MNZ from product amino-MNZ in envisioned MRI approaches at clinically relevant magnetic fields.

Polyamide (PA) membranes are widely utilized in desalination and water treatment applications, yet the mechanisms underlying water transport within these amorphous polymer materials remain insufficiently understood. To gain more insight into these problems on a microscopic scale, we employ molecular dynamics (MD) simulations to analyze the relationship between the structural properties and the water permeation behavior of PA membranes. Two distinct atomistic models of PA membranes are developed by controlling their degrees of cross-linking (DC). We then conducted a comparative analysis on their microscopic structural properties and configurations of water inside the membranes and investigated how these differences lead to different water diffusion coefficients. Our results reveal that the membrane with a lower DC exhibits higher polymer mobility and a more orderly microscopic structure, allowing the formation of pores that can hold larger water clusters as well as more transient passages between pores, both contributing to an increased water diffusion coefficient. From these observations, we can conclude that water permeability within PA membranes is governed by both the morphology of semirigid pores and the oscillatory movements of the polymer chains. Overall, these findings contribute to a deeper understanding of the intricate mechanisms governing water permeation in PA membranes and may inform the design of more efficient membranes for reverse osmosis and other water treatment technologies.

There is sufficient evidence to prove that microemulsions can be formed by two immiscible liquids (generally called oil and water components) in the presence of an amphi-solvent rather than traditional surfactants, but how to explain such surfactant-free microemulsions (SFMEs) with thermodynamics is still a challenge. In this work, based on the Flory–Huggins theory, a general thermodynamic principle for SFMEs was established, by assuming SFMEs to be a pseudobinary system consisting of the water-rich and oil-rich components (i.e., the water-rich and oil-rich phases) and considering the curvature dependence of the enthalpy of dispersion between the two pseudocomponents. A new parameter, called the two-phase interaction parameter, was introduced. The thermodynamic model can predict the SFME region in the ternary phase diagram as well as the droplet size and type of SFMEs formed. The formation and stability of SFMEs are attributed to the balance between the entropy and enthalpy of dispersion of the two phases. The rationality of the thermodynamic principle suggested here was confirmed by the experimental results of the ternary mixture of n-butanol (oil), ethanol (amphi-solvent), and water. This work provides a thermodynamic explanation for SFMEs, which can deepen our understanding of the nature of SFMEs.

Under conditions that are close to the real cellular environment, the human telomeric single-stranded overhang (∼200 nt) consisting of tens of TTAGGG repeats tends to form higher order structures of multiple G-quadruplex (G4) blocks. On account of the higher biological relevance of higher order G4 structures, ligand compounds binding to higher order G4 are significant for the drug design toward inhibiting telomerase activity. Here, we study the interaction between a cationic porphyrin derivative, 5,10,15,20-tetra{4-[2-(1-methyl-1-piperidinyl)propoxy]phenyl}porphyrin (T4), and a human telomeric G4-dimer (AG₃(T₂AG₃)₇) in the mimic intracellular molecularly crowded environment (PEG as a crowding agent) and K⁺ or Na⁺ solution (i.e., K⁺-PEG and Na⁺-PEG), by means of multiple steady-state and time-resolved spectroscopic techniques. It is revealed that the long-armed T4 selectively binds to the K⁺-PEG G4-dimer by intercalating into the cleft pocket between the two G4 blocks, since the two G4 monomers with parallel-stranded topology are stacked by head-to-tail arrangement and can offer π-stacking interface binding with T4. In contrast, the Na⁺-PEG G4-dimer with antiparallel-stranded topology adopts side-by-side arrangement of G-quartets, resulting in a lack of π-π binding sites to stabilize T4 within the cleft, and no obvious binding characteristics are observed. Interestingly, it is observed that protonation of T4 is facilitated upon binding with the K⁺-PEG G4-dimer, which can occur under physiological pH, due to the π-π stacking with two G-quartet planes that enhances the electron-rich character of the central porphyrin core of T4. Afterward, the protonated T4 displays dramatically different spectral characteristics (Soret band, Q-band, fluorescence band, and lifetime), which in turn serves as a spectral reporter for characterizing the DNA-binding event. These findings provide a mechanistic basis for developing targeted ligands that can specifically interact with higher order physiological G4 structures.