The Journal of Physical Chemistry B最新文献

G-quadruplexes (G4s) are four-stranded structures formed by guanine-rich sequences. While their structures, properties, and applications have been extensively studied, an understanding of their folding processes remains limited. In this study, we investigated the folding of the sequence d[(G₃T₂)₃G₃] in potassium solutions, focusing on the impact of a folding intermediate on the overall folding process. Our results indicate that this sequence eventually folds into a parallel G4 structure, either directly or through an antiparallel conformation intermediate, suggesting the existence of a specific competitive folding process. Detailed kinetic analysis using stopped-flow techniques reveals that the antiparallel conformation forms much faster than the parallel one. This antiparallel G4 slowly converts to the thermodynamically favored parallel topology, thus slowing the overall folding rate. As a result, the formation of the parallel quadruplex via an antiparallel G4 intermediate is slower than the direct process, indicating that this antiparallel conformation negatively impacts the overall folding process in a temperature-dependent manner. Interestingly, sodium was shown to facilitate the conversion from antiparallel to parallel. These analyses highlight the complexity of the G4 folding process, which is crucial for most biological applications.

Ionic liquids have been shown to form extended ordered structures near surfaces and in bulk. Identifying fundamental driving force(s) for this organization has been elusive. In this paper, we test a hypothesis that the ionic liquid asymmetry, inherent in many of the IL formulations to frustrate crystallization, is a significant contributor to the observed ordering. We have carried out measurements to track the ordering of ionic liquids composed of “spherical” cations, namely, tetraoctylphosphonium ([P8888]) and tetra(propoxymethyl)phosphonium [P(3O1)4] paired with tetracyanoborate anion [B(CN)4]. Analysis of the infrared signatures for films of these ionic liquids shows very little evidence of ordered structures. These liquids instead remain in a more isotropic environment even when confined to volumes of few micrometer dimensions.

Colvars is an open-source C++ library that provides a modular toolkit for collective-variable-based molecular simulations. It allows practitioners to easily create and implement descriptors that best fit a process of interest and to apply a wide range of biasing algorithms in collective variable space. This paper reviews several features and improvements to Colvars that were added since its original introduction. Special attention is given to contributions that significantly expanded the capabilities of this software or its distribution with major MD simulation packages. Collective variables can now be optimized either manually or by machine-learning methods, and the space of descriptors can be explored interactively using the graphical interface included in VMD. Beyond the spatial coordinates of individual molecules, Colvars can now apply biasing forces to mesoscale structures and alchemical degrees of freedom and perform simulations guided by experimental data within ensemble averages or probability distributions. It also features advanced computational schemes to boost the accuracy, robustness, and general applicability of simulation methods, including extended-system and multiple-walker adaptive biasing force, boundary conditions for metadynamics, replica exchange with biasing potentials, and adiabatic bias molecular dynamics. The library is made available directly within the main distributions of the academic software GROMACS, LAMMPS, NAMD, Tinker-HP, and VMD. The robustness of the software and the reliability of the results are ensured through the use of continuous integration with a test suite within the source repository.

We have shown that palladium-catalyzed cascade processes provide modular access to rigid quinoline-containing tetracyclic amines. This modular approach enables fine-tuning of the through-space charge transfer (TSCT) state formation between the lone pair localized on the nitrogen atom in the cage moiety and the quinoline moiety by variation of both the intramolecular N-aryl distance and quinoline substitution. Decreasing this N-aryl distance enhances the formation of the TSCT species, giving control over the emission color and photoluminescence quantum yield. Methoxylation of the quinoline unit decreases the propensity of TSCT formation. The development of this structure–activity relationship provides great insight for TSCT formation with an impact on further understanding dimeric, excimeric, and exciplex species. This understanding is crucial for the work underpinning their use in biosensor applications, and the conclusions are of relevance to the broader field of photoluminescence.

In this work, we propose a shear-driven nanofluidic system for energy harvesting/conversion. The system consists of a nanochannel formed by two parallel walls, where the lower wall is negatively charged, while the upper wall is neutral. The motion of the upper wall caused by a shear force drives the solution in the fluidic system to move, which generates an ionic current due to the migration of excess cations in the system. Molecular dynamics simulations demonstrate that the efficiency of the system is affected by the wall charge density, shearing stress, channel height, and binding energy of the walls. The effects of these factors on the efficiency are studied. In particular, it is shown that a high binding energy for the upper wall (e.g., hydrophilic wall) can reduce the flow slip at the upper wall and effectively transfer energy from the wall to the fluid. For the lower wall, a low binding energy, which corresponds to a hydrophobic wall, can reduce the friction at the wall, enhance the flow velocity, and improve the energy conversion efficiency. By varying these parameters, it is found that the maximum energy conversion efficiency of the system reaches 65.8%, which is the highest compared with previous systems. The underlying mechanisms are explained using the slip length at the walls, wall velocity, and charge density profiles. The system proposed in this work provides insights into the design of nanofluidic systems for energy harvesting/conversion.

Atomistic simulations of peptoids have the capability to predict structure–property relationships, depending on the accuracy of the associated force field. This work presents an addendum to the CGenFF-NTOID peptoid force field for aliphatic side chains. We develop parameters for two aliphatic side chains, R_N1-tertiary butylethyl glycine (r1tbe) and S_N1-tertiary butylethyl glycine (s1tbe). Enhanced sampled (well-tempered metadynamics) atomistic simulations are performed using CGenFF-NTOID to determine the monomer structural preferences for these side chains. The free energy minima attained through these simulations are compared with structural observations obtained from experiments. We also compare the structural preferences of aliphatic s1tbe and aromatic S_N1-naphthylethyl glycine (s1ne). This is done through parallel bias metadynamics on monomers and pentamers of s1tbe and s1ne. The structural observations through simulations are also compared with available experimental metrics of the dihedral angles and pitch. The pentamer minima structures are also compared with ab initio optimized structures, which show excellent agreement. This comparison illustrates alternatives to aromatic side chains that can be used to stabilize peptoid secondary structures. The developed parameters help to increase the diversity of peptoid side chains available for materials discovery through computational studies.

The surface protein hemagglutinin (HA) of the influenza virus plays a pivotal role in facilitating viral infection by binding to sialic acid receptors on host cells. Its conformational state is pH-sensitive, impacting its receptor-binding ability and evasion of the host immune response. In this study, we conducted extensive equilibrium microsecond-level all-atom molecular dynamics (MD) simulations of the HA protein to explore the influence of low pH on its conformational dynamics. Specifically, we investigated the impact of protonation on conserved histidine residues (H106₂) located in the hinge region of HA2. Our analysis encompassed comparisons between nonprotonated (NP), partially protonated (1P, 2P), and fully protonated (3P) conditions. Our findings reveal substantial pH-dependent conformational alterations in the HA protein, affecting its receptor-binding capability and immune evasion potential. Notably, the nonprotonated form exhibits greater stability compared to protonated states. Conformational shifts in the central helices of HA2 involve outward movement, counterclockwise rotation of protonated helices, and fusion peptide release in protonated systems. Disruption of hydrogen bonds between the fusion peptide and central helices of HA2 drives this release. Moreover, HA1 separation is more likely in the fully protonated system (3P) compared to nonprotonated systems (NP), underscoring the influence of protonation. These insights shed light on influenza virus infection mechanisms and may inform the development of novel antiviral drugs targeting HA protein and pH-responsive drug delivery systems for influenza.

Fluorescence correlation spectroscopy (FCS) measurements are performed on the ionic liquid (IL), tetradecyl(trihexyl) phosphonium chloride, [P66614⁺][Cl^–], using fluorescent probes of varying sizes: ATTO 532, ∼2 nm; and 20- and 40 nm fluorescent beads. The fluorescence correlation function, G(t), is analyzed in terms of a distribution of diffusion coefficients using a maximum entropy method (MEM). For ATTO 532 and the 20 nm beads, the fit to G(t) yields two well-defined distributions; for the 40 nm beads, however, only one is obtained. These results are consistent with the existence of two nanodomains whose size is greater than or equal to 20 nm and less than 40 nm. The origin of such nanodomains is attributed to a liquid–liquid phase transition. Other groups have observed liquid–liquid phase transitions experimentally in a number of systems, including [P66614⁺][Cl^–]. We suggest that because large regions (i.e., greater than 1–2 nm) resulting from the liquid–liquid phase transition would be expected to have different properties, such as viscosity, and because their presence would necessarily increase the number of interfaces in the IL, these regions may provide an explanation for the exceptional behavior of ILs in various separation systems.

The original method for the preparation of high-molecular-weight polyalkylene sulfides was reported. Assuming anomalous peculiarities of the reaction (high polymerization rates, high degrees of polymerization, and huge discrepancy between the expected M_n values and the experimentally obtained values), the priority task was set to study the mechanism underlying the observed new type of polymerization. Thus, it was demonstrated that xanthate and related molecules could act as pure catalysts, facilitating both the chain-growth polymerization (ring-opening of episulfides) realized via an anionic route and the direct attack of the sulfur atom of one episulfide molecule on the methylene carbon atom of the second (neighbor) episulfide molecule, accompanied by the subsequent formation of a stable thiiranium-based zwitterionic adduct. The role of xanthate and related compounds as catalysts and stabilizing particles was further supplemented by modeling the attack of thiolate on the sulfur atom of a thiiranium-based adduct. The xanthate molecule acting as a catalyst was found to be involved in all stages of the process discussed by sharing the potassium atom with the sulfur atoms of active components of the system (the initial episulfide molecule, thiolate, and the zwitterionic intermediate). The subsequent analysis revealed the exceptional transparency of the materials obtained, which was found to exceed 99%. The pronounced self-healing ability was also found to be a distinctive feature of the synthesized high-molecular-weight polyalkylene sulfides enriched with disulfide bonds.

Glycans exhibit significant structural diversity due to the flexibility of glycosidic bonds linking their constituent monosaccharides and the formation of numerous hydrogen bonds. The present work searches a simulated ensemble of glycan chain conformations attached to the catalytic domain of N-glycosylated human carbonic anhydrase IX (HCA IX-c) to identify conformations pointed away or back-folded toward the protein surface guided by different amino acid residues. A series of classical molecular dynamics (MD) simulation studies for a total of 30 μs followed by accelerated MD simulations for a total of 2 μs have been performed using two different force fields to capture varying degrees of fluctuations of both glycan chain and HCA IX. From the underlying free energy profile and kinetics derived using hidden Markov state model, several stable glycan orientations are identified that extend away from the protein surface and convert among each other with rate constants of the order 10⁷–10¹⁰ _S^–1. Most importantly, we have identified a rare glycan conformation which reaches close to a catalytically important amino acid residue, Glu-106. We further enlist the protein residues that couple such less frequent event of the glycan chain back-folding toward the surface of the protein.