The Journal of Physical Chemistry B最新文献

The interaction of protein with nanoparticles (NPs) of varying shape and/or size boosts our understanding on their bioreactivity and establishes a comprehensive database for use in medicine, diagnosis, and therapeutic applications. The present study explores the interaction between lysozyme (LYZ) and different NPs like graphene oxide (GO) and zinc oxide (ZnO) having various shapes (spherical, 's', and rod-shaped, 'r') and sizes, focusing on their binding dynamics and subsequent effects on both the protein fibrillation and antimicrobial properties. Typically, GO is considered a promising medium due to its apparent inhibition and prolonged lag phase for LYZ fibrillation. However, the present results showed that spherical ZnO NPs (sZnO) offer superior efficacy in modulating fibrillation with an extended lag time of about 158.70 h, further emphasizing the importance of detailed investigation on the nanomaterial characteristics and fibril formation kinetics beyond initial observations. The experimental findings further confirmed a strong correlation between the binding affinity of NPs to the native protein and their effective inhibition of protein denaturation, ultimately preventing fibril formation. Interestingly, the lysozyme nanoconjugates showed intriguing bactericidal effects, as confirmed through the agar plate assay and SEM imaging, over the native protein. Overall, this study shows that appropriate bionanomaterials can exhibit multifunctional properties, which paves the way for a deeper investigation of NP characteristics, ultimately benefiting a wide array of intriguing research.

Nonplanar (butterfly-shaped) phenothiazine (PTZ) and its derivative's (M-PTZ) photophysical and spectral properties have been tuned by varying the solvents and their polarity and investigated employing spectroscopic techniques such as UV-Vis, steady-state and time-resolved fluorescence, and TDDFT calculations. The UV-Vis absorption studies and TDDFT calculations reveal two distinct bands for both compounds: a strong π-π* transition at shorter wavelengths and a weaker n-π* transition, which displays a little bathochromic shift in polar solvents. The detailed emission studies reveal that such dual emission is a result of the photoinduced excited-state conjugation enhancement (ESCE) process. The band at a shorter wavelength corresponds to the locally excited (LE) state, while the longer wavelength band arises from the planarized excited state resulting from ESCE. With the increase in solvent polarity, the LE band is less affected, whereas strong positive solvatochromism is observed for the ESCE band. As the solvent polarity increases, the ESCE band demonstrates significant positive solvatochromism, while emission intensity decreases with higher solvent polarity, suggesting stabilization of the excited state. The biexponential decay of fluorescence lifetimes further corroborates the dual emission behavior of PTZ and M-PTZ. PTZ exhibits a higher photoluminescence quantum yield (PLQY) than that observed for M-PTZ, and the solvent viscosity influences the PLQY, indicating that nonradiative decay is activated during the planarization of the excited state, also known as excited-state conjugation enhancement. Furthermore, the (time-dependent) density functional theory (TD) DFT calculations performed to understand the geometrical parameters and the electronic transitions of these model molecules further corroborate experimental findings. These findings underscore the significant influence of solvent polarity and molecular structure on the dual emission and excited-state dynamics of PTZ and M-PTZ, which eventually hold substantial implications for advanced photophysical applications.

It is widely believed that the aggregation of amyloid β (Aβ) peptides into soluble oligomers is the root cause behind Alzheimer's disease. In this study, we have performed room-temperature molecular dynamics (MD) simulations of aggregated Aβ oligomers of different sizes (pentamer (O(5)), decamer (O(10)), and hexadecamer (O(16))) in binary aqueous solutions containing 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF₄]) ionic liquid (IL). Investigations have been carried out to obtain a microscopic understanding of the effects of the IL on the dynamic environment around the exterior surfaces and within the confined nanocores of the oligomers. The calculations revealed that in contrast to nearly uniform dynamics near the exterior surface, heterogeneous structural distortions of oligomers of varying sizes and nonuniform distributions of water and IL components within their core volumes modify the core dynamics in a differential manner. It is demonstrated that increasingly restricted mobility of water and IL components is the origin behind the longer time scale of dynamic heterogeneity in and around the oligomers. Importantly, due to the equivalent nondirectional nature of the B-F bonds, BF₄^- anions are found to reorient on a time scale faster than that of water molecules. Further, the structural relaxation of protein-anion (PA) hydrogen bonds around the oligomers has been found to be correlated with sluggish translational motions of the anions but anticorrelated with their reorientational time scale. In addition, it is quantified that compared to the pure aqueous medium, strengthening of protein-water (PW) hydrogen bonds in the presence of the IL leads to their longer lifetimes.

Structural, thermal, and dynamic properties of four deep eutectic solvents comprising choline chloride paired with ortho-phenolic derivative hydrogen-bond donors were probed using experiments and molecular simulations. The hydrogen-bond donors include phenol, catechol, o-chlorophenol, and o-cresol, in a 3:1 mixture with the hydrogen-bond acceptor choline chloride. Density, viscosity, and pulsed-field gradient NMR diffusivity measurements were conducted over a range of temperatures. Classical and ab initio molecular dynamics simulation results match experimental data reasonably well. The simulation results were then used to perform a more detailed analysis of the local structure and dynamics of these systems.

We here explore confinement-induced assembly of whey protein nanofibrils (PNFs) into microscale fibers using microfocused synchrotron X-ray scattering. Solvent evaporation aligns the PNFs into anisotropic fibers, and the process is followed in situ by scattering experiments within a droplet of PNF dispersion. We find an optimal temperature at which the order parameter of the protein fiber is maximized, suggesting that the degree of order results from a balance between the time scales of the forced alignment and the rotational diffusion of the fibrils. Furthermore, the assembly process is shown to depend on the nanoscale morphology and flexibility of the PNFs. Stiff/straight PNFs with long persistence lengths (∼2 μm) align at the air-water interface, with anisotropy decreasing toward the center of the droplet as Marangoni flows increase entanglement toward the center. By contrast, flexible/curved PNFs with shorter persistence lengths (<100 nm) align more uniformly throughout the droplet, likely due to enhanced local entanglements. Straight PNFs pack tightly, forming smaller clusters with short intercluster distances, while curved PNFs form intricate, adaptable networks with larger characteristic distances and more varied structures.

Fluid-silica interfaces are ubiquitous in chemistry, occurring in both natural geochemical environments and practical applications ranging from separations to catalysis. Simulations of these interfaces have been, and continue to be, a significant avenue for understanding their behavior. A constraining factor, however, is the availability of accurate force fields. Most simulations use traditional "mixing rules" to determine nonbonded dispersion interactions, an approach that has not been critically examined. Here, we present Lennard-Jones parameters for the interaction of carbon dioxide with silica interfaces that are optimized to reproduce density functional theory (DFT)-based binding energies. The modeling is based on the recently developed silica-DDEC force field, whose atomic charges are consistent with DFT calculations. Standard mixing rules are found to predict weaker CO₂ binding to silica than that obtained from DFT, an effect corrected by the optimized parameters given here. This behavior extends to other silica force fields (Clayff and Gulmen-Thompson), and the present Lennard-Jones parameters improve their performance as well. The effects of improved Lennard-Jones parameters on the structural and dynamical properties of condensed CO₂ in silica slit pores are also examined.

This study extends previous research, particularly focusing on patented scientific objects No. ID: PL 240 353 B1, investigating the physicochemical properties of the methyl 3-azido- and 3-amino-2,3-dideoxysaccharides with a nucleoside scaffold similar to 3'-azidothymidine (AZT). The study utilizes multiwavelength spectrophotometric and potentiometric methods to evaluate the ionization of the saccharide units in aqueous solutions. pK_a values, obtained from two independent methods, reveal significant sugar ionization effects on UV spectra with varying pH levels. Stability constants for divalent metal ion complexes (Cu²⁺ and Ni²⁺) with the saccharide isomers indicate that complex stoichiometries and stabilities are highly dependent on the configuration of sugar ring substituents. Spectrophotometric results show a descending order of CT-DNA-binding affinity: BRNH₂OMe > BRN₃OMe > ARN₃OMe > ARNH₂OMe, suggesting varied interaction strengths. Molecular docking of models of synthesized O-glycosides confirmed their potential as reverse transcriptase inhibitors. Among the derivatives tested, the compound BRN₃OMe displays the highest interaction with the enzyme active site residues and DNA, suggesting it may possess the greatest efficacy. Our reported results highlight the promising inhibitory properties of novel O-glycosides against HIV reverse transcriptase, supporting their potential development as antiviral agents.

The folding of the guanine repetitive region in the telomere unit into G-quadruplex (G4) by drugs has been suggested as an alternative approach for cancer therapy. Hydroxychloroquine (HCQ) and chloroquine (CQ) are two important drugs in the trial stage for cancer. Both drugs can induce the folding of telomere-guanine-rich sequences into G4 even in the absence of salt. However, the guanine repetitive telomeric sequences are always flanked by other nucleobases at both the terminal (5' or 3') that can affect the drug-induced folding pathways and stability of the G4 significantly. Hence, in this study, the HCQ and CQ drug-induced folding of the guanine repetitive telomeric sequences into G4 and its stability by varying the chemical nature, number, and positions of the flanking nucleobases has been explored using several biophysical techniques and docking studies. It has been found that the drug-induced folding of telomere with single flanking nucleobases is similar to that without flanking nucleobases irrespective of the chemical nature and position of the flanking nucleobase. However, the propensity of the folding and the stability of the telomeric G4 induced by drugs decrease significantly with the increase of the flanking nucleobases more than one of any chemical nature and position. The data suggest that the number of flanking nucleobases rather than their chemical nature and location is a critical factor in the folding of the telomere into G4 induced by both drugs. Further, it has been observed that both drugs mainly interact with the G-tract and thymine of the loop region rather than the flanking nucleobases of the telomeric sequences without or with one flanking nucleobase. In contrast, the flanking nucleobases also participate in the interaction with the HCQ and CQ along with the core guanine repeat telomeric unit in the case of the telomeric sequences with more than one flanking nucleobases. The participation of the flanking nucleobases in the interaction with the HCQ and CQ affects the hydrogen bonding of the positively charged side chain of drugs with G quartet and loop nucleobases of telomere along with the with π···π and C-H···π weak interactions between the quinoline part of the drugs with the core telomeric guanine repeat unit which affects the folding pattern of the telomere sequences with more than one flanking nucleobases into G4.

Single-molecule fluorescence resonance energy transfer (smFRET) has emerged as a pivotal technique for probing biomolecular dynamics over time at nanometer scales. Quantitative analyses of smFRET time traces remain challenging due to confounding factors such as low signal-to-noise ratios, photophysical effects such as bleaching and blinking, and the complexity of modeling the underlying biomolecular states and kinetics. The dynamic distance information shaping the smFRET trace powerfully uncovers even transient conformational changes in single biomolecules both at or far from equilibrium, relying on trace idealization to identify specific interconverting states. Conventional trace idealization methods based on hidden Markov models (HMMs) require substantial a priori knowledge of the system under study, manual intervention, and assumptions about the number of states and transition probabilities. Here, we present a deep learning framework using long short-term memory (LSTM) to automate the trace idealization, termed Kin-SiM. Our approach employs neural networks pretrained on simulated data to learn high-order correlations in the multidimensional FRET trajectories. Without user input of Markovian assumptions, the trained LSTM networks directly idealize the FRET traces to extract the number of underlying biomolecular states, their interstate dynamics, and associated kinetic parameters. On benchmark smFRET data sets, Kin-SiM achieves a performance similar to conventional HMM-based methods but with less hands-on time and lower risk of bias. We further systematically evaluate the key training factors that affect network performance to define the correct hyperparameter tuning for applying deep neural networks to smFRET data analyses.

The emergence of nanopores in two-dimensional (2D) nanomaterials offers an attractive solid-state platform for high-throughput and low-cost DNA sequencing. However, several challenges remain to be addressed before their wide application, including the too-fast DNA translocation speed (compared to state-of-the-art single nucleoside detection techniques) and too large noise/signal ratios due to DNA fluctuations inside the nanopores. Here, we use molecular dynamics (MD) simulations to demonstrate the feasibility of utilizing RNA-DNA interactions in modulating DNA translocations in 2D MoS₂ nanopores. By constructing a transmembrane-RNA-oligonucleotide-decorated nanopore (TOD nanopore), we find that the translocation speed of DNA can be significantly slowed in a sequence-dependent manner, with up to 160-fold deceleration compared with the naked control. The strong interactions between the translocating DNA and the first and second guanines of transmembrane RNAs are thought to play a key role in regulating the translocation process. Moreover, the observed suppression of base conformational fluctuations within the TOD nanopore can further improve the single nucleotide detecting resolution. Therefore, our investigations demonstrate that the proposed TOD nanopore can be a potential candidate for enhanced DNA sequencing with solid-state nanopores.