The Journal of Physical Chemistry B最新文献

The chemistry of molten salts has attracted great research interest owing to their wide applications in diverse fields. In the pyrochemical reprocessing of spent nuclear fuel or molten salt nuclear reactors, lanthanide elements as the principal fission products bring about changes in the composition and properties of molten salts. Herein, we report a comprehensive study on the coordination chemistry of the representative trivalent lanthanide ions (La³⁺/Nd³⁺) in LiCl–KCl–CsCl using a multiscale strategy combining Raman spectroscopy, deep learning, and large-scale molecular dynamics (MD) simulations. The neural network potential (NNP)-based MD and Raman spectroscopy studies revealed that La³⁺/Nd³⁺ ions prefer to form persistent octahedron complexes with the six-coordinated species as the dominant species at high temperatures. Compared to LaCl₆^3–, NdCl₆^3– shows higher stability with obviously longer lifetimes in LiCl–KCl–CsCl, as confirmed by the observed stronger interaction of Nd³⁺–Cl^– pairs. The total and partial structure factors further indicated the formation of a more stable network structure in LiCl–KCl–CsCl containing NdCl₃. Besides, the temperature exerts a larger influence on the local structures of the La³⁺ species compared to the Nd³⁺ analogues. According to the potential mean force calculations, the bond dissociation energies follow the order Ln–Cl > Li–Cl > K–Cl > Cs–Cl in LiCl–KCl–CsCl–LnCl₃. The NNP-based large-scale MD simulations have been verified to be an efficient and powerful way in molten salt chemistry research.

This study reports a comprehensive analysis and comparison of several AlphaFold2 adaptations and OmegaFold and AlphaFlow approaches in predicting distinct allosteric states, conformational ensembles, and mutation-induced structural effects for a panel of state-switching allosteric ABL mutants. The results revealed that the proposed AlphaFold2 adaptation with randomized alanine sequence scanning can generate functionally relevant allosteric states and conformational ensembles of the ABL kinase that qualitatively capture a unique pattern of population shifts between the active and inactive states in the allosteric ABL mutants. Consistent with the NMR experiments, the proposed AlphaFold2 adaptation predicted that G269E/M309L/T408Y mutant could induce population changes and sample a significant fraction of the fully inactive I₂ form which is a low-populated, high-energy state for the wild-type ABL protein. We also demonstrated that other ABL mutants G269E/M309L/T334I and M309L/L320I/T334I that introduce a single activating T334I mutation can reverse equilibrium and populate exclusively the active ABL form. While the precise quantitative predictions of the relative populations of the active and various hidden inactive states in the ABL mutants remain challenging, our results provide evidence that AlphaFold2 adaptation with randomized alanine sequence scanning can adequately detect a spectrum of the allosteric ABL states and capture the equilibrium redistributions between structurally distinct functional ABL conformations. We further validated the robustness of the proposed AlphaFold2 adaptation for predicting the unique inactive architecture of the BSK8 kinase and structural differences between ligand-unbound apo and ATP-bound forms of BSK8. The results of this comparative study suggested that AlpahFold2, OmegaFold, and AlphaFlow approaches may be driven by structural memorization of existing protein folds and are strongly biased toward predictions of the thermodynamically stable ground states of the protein kinases, highlighting limitations and challenges of AI-based methodologies in detecting alternative functional conformations, accurate characterization of physically significant conformational ensembles, and prediction of mutation-induced allosteric structural changes.

The global prevalence of dengue virus (DENV), a widespread flavivirus, has led to varied epidemiological impacts, economic burdens, and health consequences. The alarming increase in infections is exacerbated by the absence of approved antiviral agents against the DENV. Within flaviviruses, the NS3/NS2B serine protease plays a pivotal role in processing the viral polyprotein into distinct components, making it an attractive target for antiviral drug development. In this study, machine-learning (ML) techniques were employed to build predictive models for the screening of a library containing 32,000 protease inhibitors. Utilizing GNINA for structure-based virtual screening, the top potential candidates underwent a subsequent evaluation of their absorption, distribution, metabolism, excretion, and toxicity properties. Selected compounds were subjected to molecular dynamics simulations and binding free energy calculations via MM/GBSA. The results suggest that comp530 possesses binding potential to DENV protease as a noncovalent inhibitor with multiple positions for chemical substitutions, presenting opportunities for optimizing their selectivity and specificity. However, other compounds predicted via ML models may still provide a promising start for covalent inhibitors.

The optical quantum control has been successfully applied in modulating biological processes such as energy transfer and bond isomerization. Among the reactions in realizing biological functions, the electron transfer (ET) process is fundamental; hence, the quantum control over such an ET reaction is of far-reaching significance. Here, we realized optical quantum control over ultrafast ET processes in a protein, flavodoxin, by applying various chirped excitation pulses. We observed the wavepacket dynamics within a dephasing time of less than 1 ps. Within this time window, we found that the ultrafast photoinduced ET reaction can be controlled by different chirped excitations with a rate change by a factor of about 2. Furthermore, the control effect is propagated into the subsequent ultrafast back ET reaction, showing a variation of the BET dynamics with different excitation chirps. The underlying mechanism is the initial wavepacket dynamics; the differently prepared wavepackets with chirped excitation evolve along various pathways, resulting in the changes of ET rates. The successful demonstration of optical quantum control of ultrafast biological ET is significant and opens a new avenue to explore the quantum control of real biological ET reactions.

Solid polymer matrixes can modulate the electronic states of embedded chromophores and have been widely used in flexible optoelectronic and optical materials. Luteolin is one of the most common natural flavonoids, and its neutral and monodeprotonated forms are nonemissive in aqueous solution induced by ultrafast excited-state proton transfer (ESPT) followed by nonradiative relaxation. In this study, we have incorporated luteolin into poly(vinyl alcohol) (PVA) films and studied their fluorescence behaviors. Neutral and one monodeprotonated luteolin coexist in the PVA film. Weak steady-state fluorescence of neutral luteolin peaking at about 440 nm is observed for the first time. In addition, the monodeprotonated luteolin in PVA film exhibits obvious fluorescence peaking at 500 nm, with a fluorescence quantum yield of as high as 0.4 and a fluorescence lifetime of as long as 2.4 ns. Time-dependent density functional theory calculations have determined that the ESPT of neutral luteolin is barrierless but that of monodeprotonated luteolin needs to surmount a barrier, explaining their distinct emission properties. These results indicate the modulation ability of the PVA film in both ground-state deprotonation and ESPT, broadening the application areas of the solid polymer matrix.

Metalated intact and deprotonated histidyl glycine and glycyl histidine dipeptides were investigated in the gas phase by using infrared multiple photon dissociation (IRMPD) spectroscopy with light from a free-electron laser (FEL). The dipeptides M²⁺(GlyHis), M²⁺(HisGly), [M(GlyHis-H)]⁺, and [M(HisGly-H)]⁺, where M = Zn and Cd, were probed to elucidate how the His position along the peptide chain and ligand charge state might influence the structures observed in the gas phase. Simulated annealing calculations were performed to determine energetically low-lying conformers and isomers of these structures. Quantum chemical calculations were used to optimize the structures at the B3LYP level of theory using the 6-311+G(d,p) and def2-TZVP basis sets for zinc and cadmium complexes, respectively. IRMPD and calculated linear absorption spectra were compared to evaluate which structures are present. Relative energies of the various species were evaluated using single-point energy calculations for low-lying structures at the B3LYP, B3LYP-GD3BJ, ωB97XD, and MP2(full) levels using the 6-311+G(2d,2p) and def2-TZVPP basis sets. For all species, structures for both metals mirror each other, and those that reproduce the experimental spectrum were determined to be iminol structures for the intact ligands or iminol-like structures for the deprotonated ligands. Additionally, when the spectra of the deprotonated dipeptides are compared to the intact dipeptides, the change in the spectra is correlated to the group that is deprotonated.

We analyze in depth the Elastically Collective Nonlinear Langevin Equation theory of activated dynamics in metastable liquids to establish that the predicted inter-relationships between the alpha relaxation time, local cage and collective elastic barriers, dynamic localization length, and shear modulus are causally related within the theory to the medium range order (MRO) static correlation length. The latter grows exponentially with density for metastable hard sphere fluids and as a nonuniversal inverse power law with temperature for supercooled liquids under isobaric conditions. The physical origin of predicted connections between the alpha time and other metrics of cage order and the thermodynamic inverse dimensionless compressibility is fully established. It is discovered that although kinetic constraints from the real space first coordination shell are important for the alpha time, they are of secondary importance compared to the consequences of the more universal MRO correlations in both the modestly and deeply metastable regimes. This understanding sheds new light on the theoretical basis for, and prior successes of, the predictive mapping of chemically complex thermal liquids to effective hard sphere fluids based on matching their dimensionless compressibilities, a scheme we call “complexity reduction”. In essence, the latter is equivalent to the physical requirement that the thermal liquid MRO correlation equals that of its effective hard sphere analog. The mapping alone is shown to provide a remarkable level of quantitative predictive power for the glass transition temperature T_g of 21 molecular and polymer liquids. Predictions for the chemically specific absolute magnitude and growth with cooling of the MRO correlation length are obtained and lie in the window of 2–6 nm at T_g. Dynamic heterogeneity, elastic facilitation, and beyond pair structure issues are briefly discussed. Future opportunities to theoretically analyze the equilibrated deep glass regime are outlined.

X-ray crystallography is an important technique to determine the positions of atoms in a protein crystal. However, because the native environment in which proteins function, is not a crystal, but a solution, it is not a priori clear if the crystal structure represents the functional form of the protein. Because the protein structure and function often depend critically on the pH, the question arises whether proton affinities are affected by crystallization. X-ray diffraction usually does not reveal protons, which makes it difficult to experimentally measure pK_a shifts in crystals. Here, we investigate whether this challenge can be addressed by performing in silico titration with constant pH molecular dynamics (MD) simulations. We compare the computed pK_a values of proteins between solution and crystal environment and analyze these differences in the context of molecular interactions. For the proteins considered in this work, pK_a shifts were mostly found for residues at the crystal interfaces, where the environment is more apolar in the crystal than in water. Although convergence was an obstacle, our simulations suggest that in principle it is possible to apply constant pH MD to protein crystals routinely and assess the effect of crystallization on protein function more systematically than with standard MD simulations. We also highlight technical challenges that need to be addressed to make MD simulations of crystals more reliable.

Diphenylamine (DPL) has been widely utilized in industrial chemicals, but its degradation by HO^• radicals in the environment has not been fully studied yet. The present study uses quantum chemical calculations to evaluate the reaction of DPL with HO^• radicals in atmospheric and aqueous environments. The results showed that, in the atmosphere, the diphenylamine reacted with the HO^• radical rapidly, with an overall rate constant of 9.24 × 10¹¹ to 1.34 × 10¹¹ M^–1 s^–1 and a lifetime of 0.17 to 1.55 h at 253–323 K. The calculated overall rate constant in water (k_overall = 1.95 × 10¹⁰ M^–1 s^–1, pH = 3–14) is in excellent agreement with the experimental value (k_overall = 1.00 × 10¹⁰-1.36 × 10¹⁰ M^–1 s^–1). The HO^• + DPL reaction in water could occur following the hydrogen transfer (15.4%), single electron transfer (41.6%), and radical adduct formation (41.7%) mechanisms, clarifying that addition products were not exclusive products. Nevertheless, variations in temperature and pH within aqueous environments had an impact on the mechanisms, kinetics, and degradation products of the reaction of DPL with HO^• radicals.

G-quadruplexes are an important class of noncanonical secondary structures of DNA that exist in the cell and are involved in the regulation of principal genomic events. Any regulatory role of a G-quadruplex in the genome is coupled with the attendant interconversions between the G-quadruplex and duplex states. Much effort has been invested in the quest for agents that can recognize individual G-quadruplexes and shift the associated duplex-G-quadruplex equilibria toward the G-quadruplex state. In this communication, we demonstrate that, notwithstanding their simplicity, tetraalkylammonium ions, [H(CH₂)_n]₄N⁺, recognize and strongly stabilize the parallel c-MYC G-quadruplex, while not binding to the antiparallel human telomeric G-quadruplex or duplex DNA. The affinity of TAA⁺ ions for the c-MYC G-quadruplex correlates with the length of the aliphatic side chains. Our CD spectral data suggest that the binding of tetraalkylammonium ions is external, not resulting in structural changes in the host G-quadruplex. The observed discriminatory power identifies tetraalkylammonium salts as a starting point for developing topology-selective G-quadruplex-binding agents.