The Journal of Physical Chemistry B最新文献

Photoinduced vitamin D formation occurs 10-15-fold faster in phospholipid bilayers (PLB) than in isotropic solution. It has been hypothesized that amphipatic interactions of the PLB with the rotationally flexible previtamin D (Pre) stabilize its helical conformers, enhancing thermal intramolecular [1,7]-hydrogen transfer, forming vitamin D. To test this hypothesis, we carried out molecular dynamics (MD) simulations of Pre in a PLB composed of dipalmitoylphosphatidylcholine (DPPC). We designed a classical force field capable of accurately describing the equilibrium composition of Pre conformers. Using adaptive biasing force MD simulations, we determined the free energy of Pre conformers in isotropic environments (hexane and gas-phase) and in the anisotropic environment of a DPPC PLB. We find a total increase of 25.5% of the population of both helical conformers (+20.5% g+Zg+ and +5% g-Zg-) in DPPC compared to hexane. In view of ab initio simulations, showing that hydrogen transfer occurs in both helical conformers, our study strongly suggests the validity of the initial hypothesis. Regarding the amphipatic interactions of Pre with the PLB, we find that, similar to cholesterol (Chol) and 7-dehydrocholesterol (7-DHC), Pre entertains hydrogen bonds mainly to the carbonyl groups of DPPC and, to a lesser extent, with phosphate oxygen atoms and rarely to water molecules at the interface. We further report order parameters of the Pre/DPPC system, which are slightly smaller than those for Chol/DPPC and 7-DHC/DPPC, but larger than for pure DPPC. This indicates a loss in membrane viscosity upon photochemical ring-opening of 7-DHC to form Pre.

With the increasing incidence of chronic kidney disease, the effective control of protein-bound uremic toxins (PBUTs), which are difficult to remove through dialysis, has become a priority. In this study, the adsorption and diffusion behaviors of several metal-organic frameworks (MOFs) for PBUTs (indoxyl sulfate and p-cresyl sulfate) were studied by molecular dynamics (MD) simulations and umbrella sampling. For the NU series of MOFs, good correlations between the Gibbs free energy (ΔG) and the experimental clearance rates of PBUTs are found. For the adsorption behaviors, in terms of ΔG, DAJWET exhibits the best adsorption effect for indoxyl sulfate (IS), whereas NU-1000 shows the best effect for p-cresyl sulfate (pCS). Similar trends observed in the radial distribution function and mean square displacement results suggest that the π-π stacking interactions play a crucial role in the adsorption and diffusion of PBUTs by MOFs. Furthermore, it can be concluded that MOFs with highly conjugated groups (porphyrin rings and pyrene groups) tend to generate more PBUT attraction, and provide design principles for potential MOF candidates in the removal of PBUTs.

In aqueous solutions, the impact of ions on hydrogen bond networks plays a crucial role in transport properties. We used molecular dynamics simulations to explain how ions affect viscosity through structural changes. We developed a quantitative model to describe the effect of ions on viscosity. The model comprises two parts: the addition of ions alters hydrogen bond networks, and changes in hydrogen bond networks exponentially lead to changes in viscosity. The influence of ions on hydrogen bond networks involves the following mechanisms: first, ions can disrupt the tetrahedral structures within the first solvation shell into three-coordinated structures through substitution; second, structural changes within the first shells affect the global hydrogen bond network through electrostatic forces and the hindrance of ionic volumes. By analyzing the mechanisms of how hydrogen bond networks determine viscosity through the decomposition of viscosity, we found that the proportion of potential viscosity in aqueous solutions primarily increases due to the enhancement of non-hydrogen bonding interactions, and the proportion of hydrogen bonding viscosity decreases accordingly. Our results demonstrate that hydrogen bond networks are crucial for describing the changes in transport phenomena affected by external factors.

Laccases play a vital role in the degradation of toxic phenolic and aromatic amine compounds, generating considerable attention in ecological pollution remediation. However, the distinct mechanism of the laccase-catalyzed oxidation of phenols and arylamines remains unclear. Here, we examined the catalytic oxidation mechanisms of phenols and arylamines by Trametes versicolor (TvL) and Melanocarpus albomyces (MaL) laccases using molecular docking, quantum mechanics (QM), and QM/molecular mechanics (QM/MM) calculations. We docked four phenolic substrates, including 1,2-benzenediol, 2-propenylphenol, 2-methoxyhydroquinone, and 2-aminophenol, to TvL and identified their favorable reaction conformations, in which Asp206 of TvL plays an important role in binding substrates to promote the catalytic reactions. Based on the docking conformations, the QM and QM/MM calculations revealed that the oxidation reactions take place via a proton-coupled electron transfer mechanism, with proton transfer (PT) from the hydroxyl groups of substrates to the side chain of Asp206 and synchronous electron hopping from the aromatic ring of substrates to the type one copper (T1Cu) of TvL. For the MaL and 2,6-dimethoxyphenol interacting system, the oxidation reactions occur through a concerted double-proton-coupled electron transfer mechanism with a water-mediated indirect PT from the hydroxyl group of substrates to the conserved Glu235 and electron hopping from the substrate to T1Cu at the same time. The corresponding energy barriers change from 0.7 to 18.4 kcal/mol, indicating the different degradation rates of the phenols and arylamines by laccases. These findings provide insights into the oxidation mechanism of phenols and arylamines by laccases and may extend the applications of laccases.

We encounter titanium dioxide nanoparticles (TiO₂ NPs) throughout our daily lives in the form of food coloring, cosmetics, and industrial materials. They are used on a massive industrial scale, with over 1 million metric tons in the global market. For the workers who process these materials, inhalation is a major concern. The goal of our current research is to provide a direct comparison of the three major types of TiO₂ NPs (P25, E171, R101) in terms of surface characterization, cellular response, and in vivo response following introduction into the lungs of mice. In both cellular and in vivo experiments, we observe a pro-inflammatory response to the P25 TiO₂ NPs that is not observed in the E171 or R101 TiO₂ NPs at mass-matched concentrations. Cellular experiments measured a cytokine, TNF-α, as a marker of a pro-inflammatory response. In vivo experiments in mice measured the number of immune cells and four pro-inflammatory cytokines (IL-6, MIP-2, IP-10, and MCP-1) present in bronchoalveolar lavage fluid. A detailed physical and chemical characterization of the TiO₂ NPs shows that the P25 TiO₂ NPs are distinguished by smaller primary particles suggesting that samples matched by mass contain a larger number of P25 TiO₂ NPs. Cellular dose-response measurements with the P25, E171, and R101 TiO₂ NPs support this hypothesis showing increased TNF-α release by macrophages as a function of TiO₂ NP dose. Overall, this direct comparison of the three major types of TiO₂ NPs shows that the number of particles in a dose, which is dependent on the particle diameter, is a key parameter in TiO₂ NP-induced inflammation.

Although polymers are widely used in laser-irradiation research, their microscopic response to high-intensity ultrafast XUV and X-ray irradiation is still largely unknown. Here, we comparatively study a homologous series of alkenes. The XTANT-3 hybrid simulation toolkit is used to determine their damage kinetics and irradiation threshold doses. The code simultaneously models the nonequilibrium electron kinetics, the energy transfer between electrons and atoms via nonadiabatic electron-ion (electron-phonon) coupling, nonthermal modification of the interatomic potential due to electronic excitation, and the ensuing atomic response and damage formation. It is shown that the lowest damage threshold is associated with local defect creation, such as dehydrogenation, various group detachments from the backbone, or polymer strand cross-linking. At higher doses, the disintegration of the molecules leads to a transient metallic liquid state: a nonequilibrium superionic state outside of the material phase diagram. We identify nonthermal effects as the leading mechanism of damage, whereas the thermal (nonadiabatic electron-ion coupling) channel influences the kinetics only slightly in the case of femtosecond-pulse irradiation. Despite the notably different properties of the studied alkene polymers, the ultrafast-X-ray damage threshold doses are found to be very close to ∼0.05 eV/atom in all three materials: polyethylene, polypropylene, and polybutylene.

The heterodimeric sweet taste receptor, TAS1R2/1R3, is a class C G protein-coupled receptor (GPCR) that couples to gustducin (Gt), a G protein (GP) specifically involved in taste processing. This makes TAS1R2/1R3 a possible target for newly developing low caloric ligands that taste sweet to address obesity and diabetes. The activation of TAS1R2/1R3 involves the insertion of the GαP C-terminus of the GP into the GPCR in response to ligand binding. However, it is not known for sure whether the GP inserts into the TAS1R2 or TAS1R3 intracellular region of this GPCR dimer. Moreover, TAS1R2/1R3 can also connect to other GPs, such as Gs, Gi1, Gt3, Go, Gq, and G12. These GPs have different C-termini that may modify GPCR signaling. To understand the possible GP dependence of sweet perception, we use molecular dynamic (MD) simulations to examine the coupling of various GαP C20 termini to TAS1R2/1R3 for various steviol glycoside ligands and an artificial sweetener. Since the C20 could interact with the transmembrane domain (TMD) of either TAS1R2 (TMD2) or TAS1R3 (TMD3), we consider both cases. Without any sweetener, we find that the apo GPCR shows similar Go and Gt selectivities, while all steviol glycoside ligands increase the selectivity of Gt but decrease Go selectivity at TMD2. Interestingly, we find that high sweet rebaudioside M (RebM) and RebD ligands show better interactions of C20 at TMD3 for the Gt protein, but low sweet RebC and hydRebM ligands show better interaction of C20 at TMD2 for the Gt protein. Thus, our MD simulation suggests that TAS1R2/1R3 may couple the GP to either 1R2 or to 1R3 and that it can couple other GPs compared to Gt. This will likely lead to multimodal functions producing multiple patterns of intracellular signaling for sweet taste receptors, depending on the particular sweetener. Directing the GP to one of the other may have beneficial therapeutic outcomes.

Roller-coaster or undulating free energy landscapes, with alternating high and low potential cofactors, occur frequently in biological redox chains. Yet, there is little understanding of the possible advantages created by these landscapes. We examined the tetraheme subunit associated with Blastochloris viridis reaction centers, comparing the dynamics of the native protein and of hypothetical (in silico) mutants. We computed the variation in the total number of electrons in wild type (WT) and mutant tetrahemes connected to an electron reservoir in the presence of a time-varying potential, as a model for a fluctuating redox environment. We found that roller-coaster free energy landscapes buffer the redox cofactor populations from these fluctuations. The WT roller-coaster landscape slows forward and backward electron transfer in the face of fluctuations, and may offer the advantage of sustaining the reduction of essential cofactors, such as the chlorophyll special pair in photosynthesis, even though an undulating landscape introduces thermodynamically uphill steps in multistep redox chains.