The Journal of Physical Chemistry B最新文献

This study investigates the thermodynamic parameters of 1300 RNA/DNA hybrid duplexes, including both natural and chemically modified forms, using molecular dynamics (MD) simulations. Modified duplexes consist of phosphorothioate (PS) backbones and 2'-O-methoxyethyl (MOE) modifications, both commonly used in therapeutic oligonucleotides. Hybridization enthalpy and entropy were calculated from MD trajectories using molecular mechanics Poisson-Boltzmann surface area (MMPBSA) and molecular mechanics generalized Born surface area (MMGBSA) approaches. To address discrepancies with experimental data, we established empirical relationships by comparing calculated values with known experimental results of natural hybrid duplexes, then extended these relationships to the entire data set. The corrected parameters were subsequently used to generate nearest-neighbor (NN) models, allowing for experimentally reliable melting temperature predictions. In this process, MMGBSA demonstrated superior predictive performance with high convergence and consistency for both natural and modified duplexes. Specifically, MMGBSA captured the stabilizing effects of the MOE modification with minimal bias, while MMPBSA exhibited greater variability and limited reliability. These findings highlight the potential of MMGBSA for accurate thermodynamic modeling of both natural and modified nucleic acids, providing a robust framework and experimentally meaningful insights for applications in nucleic acid-based therapeutic design and biotechnology.

The viral rhodopsin 1 subfamily consists of microbial rhodopsins, such as VirChR1, with a light-gated cation channeling functionality, which is inhibited by calcium. For VirChR1, S14, E54, and N225 have been proposed as key residues for calcium binding. They form a highly conserved SEN-triad in channelrhodopsins near the functionally important central gate. Here, we present a time-resolved UV/vis spectroscopic study on the VirChR1 variants S14A, E54A, and N225A in a calcium-dependent manner. Comparison with the calcium-associated effects observed for the wild type shed light on the role of the respective residues for the calcium interaction. While S14A shows less pronounced, yet similar, signals, indicative of a reduced calcium affinity, E54A exhibits nearly calcium-independent photocycle kinetics, highlighting its crucial role for calcium binding. The N225A variant shows altered photocycle kinetics, in both the absence and presence of calcium, demonstrating its critical role in the formation of the functionally important central gate in VirChR1.

The microbial aminotransferase enzyme DapC is vital for lysine biosynthesis in various Gram-positive bacteria, including Mycobacterium tuberculosis. Characterization of the enzyme's conformational dynamics and identifying the key residues for ligand binding are crucial for the development of effective antimicrobials. This study employs atomistic simulations to explore and categorize the dynamics of DapC in comparison to other classes of aminotransferase. DapC undergoes an open-to-closed conformational change upon substrate binding, characterized by the movement of the N-terminal α2 helix, akin to that observed in the class Ib aspartate aminotransferase from Thermus thermophilus. Based on sequence similarity, essential dynamics, and the absence of the characteristic hinge movement, DapC is classified as a class Ib aminotransferase of type-I pyridoxal-5'-phosphate (PLP)-dependent enzyme. In the open state of DapC, two binding modes of glutamate, namely, canonical and alternate, separated by a dihedral rotation, are equally preferred. The closed state prefers the canonical binding mode, which is favorable for catalysis. In the case where the substrate binds in the alternate mode, a low-barrier dihedral rotation generates the canonical mode for efficient catalysis. The presence of two highly conserved residues, Phe14 and Gln31, stabilizes the closed state of substrate-bound DapC. Mutations of these residues disrupt the crucial hydrophobic interactions with the substrate, causing the enzyme to shift to an open state. While Phe14 has a dominant role, Gln31 is less consequential in regulating the conformational change, while the double mutation leads to a rapid conformation change.

Temperature-responsive macromolecules can provide insights into the mechanisms of the aggregation and precipitation processes of proteins. In this study, the PEO–PPO–PEO triblock copolymer, Pluronic P123, has been utilized as a protein model to investigate the thermally induced dynamic transition behavior by ultrasensitive differential scanning calorimetry (US-DSC). The results of US-DSC reveal hysteresis in the disaggregation process of P123 micelles. Combined with the particle size distribution, a stepwise disaggregation mechanism is proposed. The disaggregation of P123 micelles in the cooling process involved rod-to-sphere transition, fragmentation, and dissolution of micelles. Moreover, US-DSC results show that both the sphere-to-rod transition and micelle fragmentation are dependent on the scanning rate and reveal the relationship between the dynamic transition and thermodynamic properties of P123. These findings expand the understanding not only of aggregation and disaggregation of P123 in dilute aqueous systems but also of the thermal unfolding and aggregation of proteins.

Interfacial systems with spherical symmetry are ubiquitous in nature and the accurate estimation of local self-diffusion coefficients in these systems is crucial to our understanding of processes such as the partitioning of atmospheric species to aerosol droplets and water transport across cell membranes. In this work, we extend a method originally developed to estimate local diffusion coefficients in systems with flat interfaces to the spherically symmetric case. Specifically, we derive an analytical solution to the linearized Smoluchowski equation in spherical coordinates and utilize molecular dynamics simulations to obtain a parameter required to estimate the local self-diffusion coefficient from the solution. We demonstrate that the derived solution is indeed accurate by comparing it to the numerical solution and also validate that the assumptions under which our solution was derived are not too stringent. We further validate our solution by computing the local diffusion coefficients at different radial positions in bulk SPC/E water and comparing the results to the overall diffusion coefficient obtained from Einstein's mean squared displacement method. Finally, we apply the method to an SPC/E water droplet suspended in its own vapor. We observe that the diffusion coefficient increases from the center of the droplet toward the interface, a result in line with previous results reported for flat interfaces.

Understanding the structure-dynamic relationship during the glass transition remains a complex challenge. Recent studies suggest that machine learning (ML) models improve in predicting glassy dynamics when incorporating the distance from the initial to equilibrium states. However, the directional aspect of particle vibrations within the cage has been overlooked. To address this, we propose using vectorial displacement from the initial to equilibrium states as a structural input to ML models. Then, we introduce the Equivariance-Constrained Invariant Graph Neural Network (EIGNN), which uses the displacement parameter to facilitate the structural encoding of the initial configuration and equilibrium configuration. Experimental validation on a three-dimensional (3D) Kob-Andersen system from the GlassBench data set demonstrates that EIGNN significantly enhances the understanding of structure-dynamics correlations and shows robust temperature transferability. Finally, the role of displacement parameters in representing the local bond orientation order is demonstrated through a simplified version of EIGNN, referred to as EIGNN++. These findings underscore the critical role of the orientation of cage dynamics in improving the predictive power of glassy dynamics models.

The glass formation temperature range is commonly divided into a weakly supercooled regime at higher temperatures and a deeply supercooled regime at lower temperatures, with a change in the physical mechanisms that govern dynamics often postulated to occur at the crossover between these regimes. This crossover temperature T_c is widely determined based on a fit of relaxation time vs temperature data to a power law divergence form predicted by the naı̈ve mode coupling theory (MCT). Here, we show, based on simulation data spanning polymeric, small molecule organic, metallic, and inorganic glass formers, that this approach does not yield an objective measure of a crossover temperature. Instead, the value of T_c is determined by the lowest temperature T_min employed in the fit, and no regime of stationary or convergent T_c value is generally observed as T_min is varied. Nor does the coefficient of determination R² provide any robust means of selecting a fit range and thus a value of T_c. These results may require a re-evaluation of published results that have employed the fit MCT T_c value as a metric of temperature-dependent dynamics or a benchmark for depth of supercooling, and they highlight a need for the field to converge on a more objective determination of any posited crossover temperature between high and low temperature regimes of glass formation.

Highly aligned graphene aerogels (HAGA) with three-dimensional (3D) porous structures, excellent photothermal conversion ability and spectral absorption rate are considered to be a potential material to develop efficient and clean water production by utilizing solar energy solar energy. In this study, we employed molecular dynamics (MD) simulations to investigate the mechanisms of water and salt ion transport within HAGA. We also explored how the nanopore size of the network structure affects the movement behavior of water and salt ions. Improved water transport and salt ion blocking abilities were observed when the nanopore size of HAGA was smaller. Specifically, when the nanopore size was 0.83 nm, both the mobility of water and salt ions were significantly enhanced due to the single-chain phenomenon. In addition, the effects of the external temperature field on the transport process of water and salt ions within the nanoscale HAGA are also considered. It is found that the abilities of water and salt ions transport became drastic with the increase of temperature. Under the same temperature gradient, the water molecules flowed toward the heat temperature direction, however, the salt ions moved toward the cold temperature direction. These special phenomena can be explained by the thermal creep effect and the thermophoretic effect, respectively. Overall, these findings provide a more thorough understanding of the water and salt ions transport mechanisms of HAGA, which are significant for providing useful guidelines of HAGA design.

Over the last two decades, advancements in structural resolution and spectral characterization have significantly enhanced our understanding of photosynthesis. However, the complexity of photosystem (PS) supercomplexes still presents challenges. In the Rhodobacter sphaeroides reaction center (RSRC), the charge separation process begins with a charge-transfer (CT) step at the special pair (P), a dimer of bacteriochlorophyll a (BChl), which acts as the donor, and continues with electron transport through the active pigments. Our computational study explores CT rectification in RSRC. We find that the CT rate is faster in the A branch compared with the B branch, which can be attributed to the orientation of the pigments near P and the influence of the surrounding protein complex on the dielectric constant. The calculated rate constants are derived using Fermi's golden rule, with a first-principles approach that employs an optimally tuned screened range-separated hybrid functional within a polarizable continuum model (SRSH-PCM).

Cyanobacteriochromes (CBCRs) are phytochrome-related photosensors that utilize a linear tetrapyrrole (bilin) as a chromophore. Cyanobacteriochrome RcaE belongs to the green/red-type subfamily that photoconverts between green-absorbing (Pg) and red-absorbing (Pr) states. This subfamily shows a protochromic photocycle, leveraging a protonation state change at the B ring pyrrole nitrogen (N_B) to induce a large absorption shift. However, it is unclear why the deprotonation occurs at N_B among the four possible deprotonation sites (N_A to N_D), and its generality in other bilin-binding proteins remains unknown. In this study, we measured the Raman spectra of the Pg state of RcaE with isotopically labeled bilin chromophores. Vibrational analysis using quantum mechanics/molecular mechanics calculations led to a refinement of the structure of the N_B deprotonated bilin in the C5-Z,syn/C10-Z,syn/C15-Z,anti (ZZZssa) configuration. Density functional theory calculations of a series of chromophore models further revealed that N_B deprotonation most effectively minimizes the repulsion of the pyrrole NH moieties in the chromophore. Our data suggest that N_B deprotonation is a common property for the other CBCRs and phytochromes that harbor a bilin chromophore in the ZZZssa configuration and lack anionic groups interacting with the pyrroles. These findings provide new insights into the absorption tuning mechanism in the phytochrome superfamily of photosensors.